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Wladimiro Jiménez - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Aquaretic effect of the V2-AVP receptor antagonist, RWJ-351647, in cirrhotic rats with ascites and water retention.
    British journal of pharmacology, 2005
    Co-Authors: Josefa Ros, Guillermo Fernández-varo, Vicente Arroyo, Juan Rodés, Joseph W. Gunnet, Keith T. Demarest, Javier Muñoz-luque, Wladimiro Jiménez
    Abstract:

    1 A disturbance in body water homeostasis is a common feature in advanced cirrhosis. This disturbance is always associated with the existence of ascites and is characterized by an inability to adjust the amount of water excreted in the urine to the amount of water ingested. Vasopressin (AVP) is of major importance in the pathogenesis of water retention and hyponatremia in cirrhosis. 2 The current study assessed the renal, hormonal and hemodynamic effects induced by 10-day chronic oral administration of RWJ-351647 (0.5 mg kg(-1) daily), a new nonpeptide V(2)-AVP antagonist, in rats with CCl(4)-induced cirrhosis, ascites and severe water retention. Urine volume (UV), urine osmolality and sodium and potassium excretion were measured daily. At the end of the study, systemic hemodynamic parameters were also assessed. 3 Long-term administration of RWJ-351647 has an Aquaretic effect in rats with cirrhosis, ascites, water retention and hypo-osmolality. It increases UV (ANOVA: F=7.32, P

  • effect of the v1a v2 avp receptor antagonist conivaptan on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of Hepatology, 2003
    Co-Authors: Guillermo Fernandezvaro, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Pilar Cejudomartin, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of hepatology, 2003
    Co-Authors: Guillermo Fernández-varo, Josefa Ros, Pilar Cejudo-martı́n, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • long term Aquaretic efficacy of a selective nonpeptide v2 vasopressin receptor antagonist sr121463 in cirrhotic rats
    Journal of Pharmacology and Experimental Therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Manuel Moralesruiz, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (UOsmV), and sodium excretion (UNaV) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, UOsmV, and UNaV did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced UOsmV during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased UNaV without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.

  • Long-Term Aquaretic Efficacy of a Selective Nonpeptide V2-Vasopressin Receptor Antagonist, SR121463, in Cirrhotic Rats
    The Journal of pharmacology and experimental therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Manuel Morales-ruiz, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted

Vicente Arroyo - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of Two Aquaretic Drugs (Niravoline and OPC-31260) in Cirrhotic Rats with Ascites and Water Retention1
    2016
    Co-Authors: Jorge-luis Poo, Vicente Arroyo, Nuria Bordas, Alberto Leivas, Manuel Morales-ruiz, Rosa Maria Muñoz, Francisca Rivera
    Abstract:

    k-Opioid receptor agonists (niravoline) or nonpeptide antidi-uretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess Aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic ad-ministration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine vol-ume, urinary osmolality, sodium excretion, and urinary excre-tion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increase

  • Sustained Aquaretic effect of the V2-AVP receptor antagonist, RWJ-351647, in cirrhotic rats with ascites and water retention.
    British journal of pharmacology, 2005
    Co-Authors: Josefa Ros, Guillermo Fernández-varo, Vicente Arroyo, Juan Rodés, Joseph W. Gunnet, Keith T. Demarest, Javier Muñoz-luque, Wladimiro Jiménez
    Abstract:

    1 A disturbance in body water homeostasis is a common feature in advanced cirrhosis. This disturbance is always associated with the existence of ascites and is characterized by an inability to adjust the amount of water excreted in the urine to the amount of water ingested. Vasopressin (AVP) is of major importance in the pathogenesis of water retention and hyponatremia in cirrhosis. 2 The current study assessed the renal, hormonal and hemodynamic effects induced by 10-day chronic oral administration of RWJ-351647 (0.5 mg kg(-1) daily), a new nonpeptide V(2)-AVP antagonist, in rats with CCl(4)-induced cirrhosis, ascites and severe water retention. Urine volume (UV), urine osmolality and sodium and potassium excretion were measured daily. At the end of the study, systemic hemodynamic parameters were also assessed. 3 Long-term administration of RWJ-351647 has an Aquaretic effect in rats with cirrhosis, ascites, water retention and hypo-osmolality. It increases UV (ANOVA: F=7.32, P

  • effect of the v1a v2 avp receptor antagonist conivaptan on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of Hepatology, 2003
    Co-Authors: Guillermo Fernandezvaro, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Pilar Cejudomartin, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of hepatology, 2003
    Co-Authors: Guillermo Fernández-varo, Josefa Ros, Pilar Cejudo-martı́n, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • long term Aquaretic efficacy of a selective nonpeptide v2 vasopressin receptor antagonist sr121463 in cirrhotic rats
    Journal of Pharmacology and Experimental Therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Manuel Moralesruiz, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (UOsmV), and sodium excretion (UNaV) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, UOsmV, and UNaV did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced UOsmV during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased UNaV without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.

Josefa Ros - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Aquaretic effect of the V2-AVP receptor antagonist, RWJ-351647, in cirrhotic rats with ascites and water retention.
    British journal of pharmacology, 2005
    Co-Authors: Josefa Ros, Guillermo Fernández-varo, Vicente Arroyo, Juan Rodés, Joseph W. Gunnet, Keith T. Demarest, Javier Muñoz-luque, Wladimiro Jiménez
    Abstract:

    1 A disturbance in body water homeostasis is a common feature in advanced cirrhosis. This disturbance is always associated with the existence of ascites and is characterized by an inability to adjust the amount of water excreted in the urine to the amount of water ingested. Vasopressin (AVP) is of major importance in the pathogenesis of water retention and hyponatremia in cirrhosis. 2 The current study assessed the renal, hormonal and hemodynamic effects induced by 10-day chronic oral administration of RWJ-351647 (0.5 mg kg(-1) daily), a new nonpeptide V(2)-AVP antagonist, in rats with CCl(4)-induced cirrhosis, ascites and severe water retention. Urine volume (UV), urine osmolality and sodium and potassium excretion were measured daily. At the end of the study, systemic hemodynamic parameters were also assessed. 3 Long-term administration of RWJ-351647 has an Aquaretic effect in rats with cirrhosis, ascites, water retention and hypo-osmolality. It increases UV (ANOVA: F=7.32, P

  • effect of the v1a v2 avp receptor antagonist conivaptan on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of Hepatology, 2003
    Co-Authors: Guillermo Fernandezvaro, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Pilar Cejudomartin, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of hepatology, 2003
    Co-Authors: Guillermo Fernández-varo, Josefa Ros, Pilar Cejudo-martı́n, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • long term Aquaretic efficacy of a selective nonpeptide v2 vasopressin receptor antagonist sr121463 in cirrhotic rats
    Journal of Pharmacology and Experimental Therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Manuel Moralesruiz, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (UOsmV), and sodium excretion (UNaV) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, UOsmV, and UNaV did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced UOsmV during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased UNaV without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.

  • Long-Term Aquaretic Efficacy of a Selective Nonpeptide V2-Vasopressin Receptor Antagonist, SR121463, in Cirrhotic Rats
    The Journal of pharmacology and experimental therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Manuel Morales-ruiz, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted

Francisca Rivera - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of Two Aquaretic Drugs (Niravoline and OPC-31260) in Cirrhotic Rats with Ascites and Water Retention1
    2016
    Co-Authors: Jorge-luis Poo, Vicente Arroyo, Nuria Bordas, Alberto Leivas, Manuel Morales-ruiz, Rosa Maria Muñoz, Francisca Rivera
    Abstract:

    k-Opioid receptor agonists (niravoline) or nonpeptide antidi-uretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess Aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic ad-ministration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine vol-ume, urinary osmolality, sodium excretion, and urinary excre-tion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increase

  • effect of the v1a v2 avp receptor antagonist conivaptan on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of Hepatology, 2003
    Co-Authors: Guillermo Fernandezvaro, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Pilar Cejudomartin, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites
    Journal of hepatology, 2003
    Co-Authors: Guillermo Fernández-varo, Josefa Ros, Pilar Cejudo-martı́n, Carmen Cano, Vicente Arroyo, Francisca Rivera, Juan Rodés, Wladimiro Jiménez
    Abstract:

    Abstract Background : Selective V 2 -AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V 1a /V 2 -AVP antagonists are also efficacious as Aquaretic agents under these conditions. This is important, particularly considering that blockade of V 1a -AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims : To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V 1a /V 2 -AVP antagonist, Conivaptan, in rats with CCl 4 -induced cirrhosis, ascites and severe water retention. Methods : We assessed the Aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (U Na V) were measured daily. At the end of the study arterial pressure was also measured. Results : Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V 1a /V 2 -AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized U Na V without affecting creatinine clearance and arterial pressure. Conclusions : Dual V 1a /V 2 -receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.

  • long term Aquaretic efficacy of a selective nonpeptide v2 vasopressin receptor antagonist sr121463 in cirrhotic rats
    Journal of Pharmacology and Experimental Therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Manuel Moralesruiz, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (UOsmV), and sodium excretion (UNaV) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, UOsmV, and UNaV did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced UOsmV during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased UNaV without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.

  • Long-Term Aquaretic Efficacy of a Selective Nonpeptide V2-Vasopressin Receptor Antagonist, SR121463, in Cirrhotic Rats
    The Journal of pharmacology and experimental therapeutics, 2000
    Co-Authors: Wladimiro Jiménez, Josefa Ros, Carmen Cano, Vicente Arroyo, Francisca Rivera, Manuel Morales-ruiz, Claudine Serradeil-le Gal, Pilar Cejudo, Marc Pascal, Jean-pierre Maffrand
    Abstract:

    Water retention in experimental cirrhosis can be reversed by blocking V2-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the κ-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses Aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V2-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the Aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted

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  • OPC-41061, a Highly Potent Human Vasopressin V2-Receptor Antagonist: Pharmacological Profile and Aquaretic Effect by Single and Multiple Oral Dosing in Rats
    The Journal of pharmacology and experimental therapeutics, 1998
    Co-Authors: Yoshitaka Yamamura, Shigeki Nakamura, Shuji Itoh, Takahiro Hirano, Toshiyuki Onogawa, Tatsuya Yamashita, Yoshihisa Yamada, Tsujimae Kenji, Masashi Aoyama, Kounori Kotosai
    Abstract:

    The pharmacological profile and the acute and chronic Aquaretic effects of OPC-41061, a novel nonpeptide human arginine vasopressin (AVP) V2-receptor antagonist, were respectively characterized in HeLa cells expressing cloned human AVP receptors and in conscious male rats. OPC-41061 antagonized [3H]-AVP binding to human V2-receptors (Ki = 0.43 +/- 0.06 nM) more potently than AVP (Ki = 0. 78 +/- 0.08 nM) or OPC-31260 (Ki = 9.42 +/- 0.90 nM). OPC-41061 also inhibited [3H]-AVP binding to human V1a-receptors (Ki = 12.3 +/- 0.8 nM) but not to human V1b-receptors, indicating that OPC-41061 was 29 times more selective for V2-receptors than for V1a-receptors. OPC-41061 inhibited cAMP production induced by AVP with no intrinsic agonist activity. In rats, OPC-41061 inhibited [3H]-AVP binding to V1a-receptors (Ki = 325 +/- 41 nM) and V2-receptors (Ki = 1.33 +/- 0. 30 nM), showing higher receptor selectivity (V1a/V2 = 244) than with human receptors. A single oral administration of OPC-41061 in rats clearly produced dose-dependent aquaresis. In treatment by multiple OPC-41061 dosing for 28 days at 1 and 10 mg/kg p.o. in rats, significant Aquaretic effects were seen throughout the study period. As the result of aquaresis, hemoconcentration was seen at 4 hr postdosing although, no differences were seen in serum osmolality, sodium, creatinine and urea nitrogen concentrations at 24 hr postdosing. Furthermore, there was no difference in serum AVP concentration, pituitary AVP content or the number and affinity of AVP receptors in the kidney and liver at trough throughout the study period. These results demonstrate that OPC-41061 is a highly potent human AVP V2-receptor antagonist and produces clear aquaresis after single and multiple dosing, suggesting the usefulness in the treatment of various water retaining states.

  • Therapeutic and diagnostic potential of a vasopressin-2 antagonist for impaired water handling in cirrhosis.
    Clinical pharmacology and therapeutics, 1998
    Co-Authors: Tomoo Inoue, Akihiro Ohnishi, Atsushi Matsuo, Bunpei Kawai, Naoko Kunihiro, Yoshiki Tada, Fumiaki Koizumi, Tommy Chau, Keizo Okada, Yoshitaka Yamamura
    Abstract:

    Objective Progressive cirrhosis is associated with increasing difficulty to handle free water. We examined the therapeutic potential of an orally active nonpeptide vasopressin-2 receptor antagonist (OPC-31260) in the management of edema and ascites in patients with cirrhosis. By means of its chemical blockade of the vasopressin-2 receptor in the kidney, we also assessed the ability of renal water handling in the early stage of cirrhosis. Methods A single 30 mg dose of OPC-31260 was administered orally to eight biopsy-proven patients with cirrhosis who had ascites or peripheral edema. The Aquaretic responses were compared with those in six healthy subjects. Results In the patients with cirrhosis, OPC-31260 significantly (p < 0.01) increased the urinary excretion rate at 0 to 2 hours, and significantly (p < 0.01) lowered urine osmolality at 2 to 4 hours after administration. Free water clearance increased from −0.48 ± 0.14 to +0.19 ± 0.21 ml/min (p < 0.05) at 0 to 4 hours after administration. However, these Aquaretic responses in the patients with cirrhosis were only approximately half the responses observed in the healthy subjects. A significant (p < 0.05) inverse relationship was observed between indocyanine green retention at 15 minutes after administration and the maximal free water clearance after administration to the patients with cirrhosis. Urinary sodium excretion did not change significantly in the patients, whereas it increased twofold in the healthy subjects. Urinary vasopressin excretion tended to increase in the patients, whereas it increased twofold to threefold (p < 0.01 to 0.05) from the baseline in the healthy subjects. Urinary prostaglandin E2 excretion was not increased, and serum sodium and plasma vasopressin levels were elevated only slightly in both groups. Conclusions Even though a hyporesponsiveness was observed in the group of patients with cirrhosis compared with the healthy group, the novel vasopressin-2 antagonist induced hypotonic diuresis in patients with cirrhosis, suggesting a therapeutic potential in managing water excess. This drug response may be a new index to assess impairment of water handling in patients with cirrhosis. Clinical Pharmacology & Therapeutics (1998) 63, 561–570; doi:

  • orally active nonpeptide vasopressin v2 receptor antagonists a novel series of 1 4 benzoylamino benzoyl 2 3 4 5 tetrahydro 1h benzazepines and related compounds
    Journal of Medicinal Chemistry, 1996
    Co-Authors: Hidenori Ogawa, Yoshitaka Yamamura, Hisashi Miyamoto, Kazuyoshi Kitano, Michinori Tanaka, Kenji Nakaya, Shigeki Nakamura, K. Kondo, Hiroshi Yamashita, Toyoki Mori
    Abstract:

    This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv Aquaretic agent.

  • Aquaretic effect of a potent, orally active, nonpeptide V2 antagonist in men.
    The Journal of pharmacology and experimental therapeutics, 1995
    Co-Authors: Akihiro Ohnishi, Yoshitaka Yamamura, Yoshimasa Orita, Tomoo Inoue, N Takagi, T Fujita, T Toyoki, Y Ihara, Teruji Tanaka
    Abstract:

    Solute-free water diuretics (Aquaretics) that antagonize hydrosmotic vasopressin 2 (V2) receptors may be useful in treating diseases in which water is retained. An orally active, nonpeptide, selective V2 antagonist (OPC-31260) was administered in six dose steps (3, 15, 30, 60, 100 and 200 mg) to six healthy, normally hydrated men to investigate the Aquaretic effects in comparison with 12 placebo-treated control subjects (two at each dose). All subjects tolerated all six doses without serious clinical side effects. OPC-31260 increased the first 6-hr hypotonic urine volume dose-dependently. Administration at 30 mg raised the 6-hr urine volume to 2 times, 100 mg to 3 times and 200 mg to 4 times (1828.0 +/- 130.2 ml/6 hr) that of the placebo group (470.4 +/- 52.1 ml/6 hr). The drug increased urine flow maximally between 1 and 1.5 hr at all doses (e.g., 10.0 +/- 0.7-10.8 +/- 0.4 ml/min at 60-200 mg). The drug rapidly lowered urine osmolality for 4 hr, particularly between 60 and 90 min (e.g., 72.3 +/- 2.3 and 62.3 +/- 5.1 mOsm/kg at 100 and 200 mg, respectively). In marked hypotonic diuresis, mean free-water clearance of the 6-hr urine increased dose-proportionally into the positive range, reaching 2.82 +/- 0.21 ml/min at 200 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

  • A Novel Nonpeptide Selective Vasopressin 2 Antagonist (OPC-31260) in Men
    1993
    Co-Authors: Akihiro Ohnishi, Yoshitaka Yamamura, Yoshimasa Orita, Ritsuko Okahara, I Hiroaki Fujihara, Tomoo Inoue, Youichi Yabuuchi, Teruji Tanaka
    Abstract:

    Solute-free water diuretics (Aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects ofintravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses ofOPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63±2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80±0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg ofOPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent Aquaretic effect in men. (J. Clin. Invest. 1993. 92:2653-2659.) Key words: vasopressin antagonist * Aquaretic effect * urine osmolality hyponatremia * arginine vasopressin