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Veikko A Koivisto - One of the best experts on this subject based on the ideXlab platform.

  • acute administration of metoprolol and Enalaprilat reduces insulin stimulated thermogenesis and skin blood flow
    Journal of Internal Medicine, 1996
    Co-Authors: J A Tuominen, Johan G Eriksson, Veikko A Koivisto
    Abstract:

    Tuominen JA, Eriksson JG, Koivisto VA (Department of Medicine, Helsinki University Central Hospital, and National Institute of Public Health, Helsinki, Finland). Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow. J Intern Med 1996; 239: 399–406. Objective. To examine the acute effects of intravenous metoprolol and Enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Design. Randomized, single-blind, placebo-controlled trial. Setting. Helsinki University Central Hospital, Finland. Subjects. Seven moderately insulin-resistant nondiabetic subjects. Interventions. Each subject was studied three times at 2–3 weeks intervals; metoprolol (5 mg), Enalaprilat (2 mg) or saline infusions were used. Methods. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy expenditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to Enalaprilat (2.1±0.2 vs. 2.8±0.4 mL per 100 mL min-1; P<0.05). Glucose-plus-insulin-stimulated thermogenesis and total energy expenditure were reduced both by metoprolol (71 and 5.2%; P<0.05 in both) and Enalaprilat (59%, P= 0.06; and 7.6%, P<0.05) as compared to the control study. Skin blood flow (laser Doppler) increased by 100% (P<0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearm and whole-body glucose uptake was not influenced by metoprolol or Enalaprilat administration. Conclusions. (i) Both metoprolol and Enalaprilat inhibit glucose-plus-insulin-induced thermogenesis and a rise in skin blood flow. (ii) Metoprolol further reduces forearm blood flow compared to Enalaprilat. (iii) Neither drug has any acute effect on insulin sensitivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both for energy balance and thermoregulation during periods of hyperinsulinaemia in man.

  • Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow.
    Journal of Internal Medicine, 1996
    Co-Authors: J A Tuominen, Johan G Eriksson, Veikko A Koivisto
    Abstract:

    Tuominen JA, Eriksson JG, Koivisto VA (Department of Medicine, Helsinki University Central Hospital, and National Institute of Public Health, Helsinki, Finland). Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow. J Intern Med 1996; 239: 399–406. Objective. To examine the acute effects of intravenous metoprolol and Enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Design. Randomized, single-blind, placebo-controlled trial. Setting. Helsinki University Central Hospital, Finland. Subjects. Seven moderately insulin-resistant nondiabetic subjects. Interventions. Each subject was studied three times at 2–3 weeks intervals; metoprolol (5 mg), Enalaprilat (2 mg) or saline infusions were used. Methods. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy expenditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to Enalaprilat (2.1±0.2 vs. 2.8±0.4 mL per 100 mL min-1; P

J A Tuominen - One of the best experts on this subject based on the ideXlab platform.

  • acute administration of metoprolol and Enalaprilat reduces insulin stimulated thermogenesis and skin blood flow
    Journal of Internal Medicine, 1996
    Co-Authors: J A Tuominen, Johan G Eriksson, Veikko A Koivisto
    Abstract:

    Tuominen JA, Eriksson JG, Koivisto VA (Department of Medicine, Helsinki University Central Hospital, and National Institute of Public Health, Helsinki, Finland). Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow. J Intern Med 1996; 239: 399–406. Objective. To examine the acute effects of intravenous metoprolol and Enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Design. Randomized, single-blind, placebo-controlled trial. Setting. Helsinki University Central Hospital, Finland. Subjects. Seven moderately insulin-resistant nondiabetic subjects. Interventions. Each subject was studied three times at 2–3 weeks intervals; metoprolol (5 mg), Enalaprilat (2 mg) or saline infusions were used. Methods. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy expenditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to Enalaprilat (2.1±0.2 vs. 2.8±0.4 mL per 100 mL min-1; P<0.05). Glucose-plus-insulin-stimulated thermogenesis and total energy expenditure were reduced both by metoprolol (71 and 5.2%; P<0.05 in both) and Enalaprilat (59%, P= 0.06; and 7.6%, P<0.05) as compared to the control study. Skin blood flow (laser Doppler) increased by 100% (P<0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearm and whole-body glucose uptake was not influenced by metoprolol or Enalaprilat administration. Conclusions. (i) Both metoprolol and Enalaprilat inhibit glucose-plus-insulin-induced thermogenesis and a rise in skin blood flow. (ii) Metoprolol further reduces forearm blood flow compared to Enalaprilat. (iii) Neither drug has any acute effect on insulin sensitivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both for energy balance and thermoregulation during periods of hyperinsulinaemia in man.

  • Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow.
    Journal of Internal Medicine, 1996
    Co-Authors: J A Tuominen, Johan G Eriksson, Veikko A Koivisto
    Abstract:

    Tuominen JA, Eriksson JG, Koivisto VA (Department of Medicine, Helsinki University Central Hospital, and National Institute of Public Health, Helsinki, Finland). Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow. J Intern Med 1996; 239: 399–406. Objective. To examine the acute effects of intravenous metoprolol and Enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Design. Randomized, single-blind, placebo-controlled trial. Setting. Helsinki University Central Hospital, Finland. Subjects. Seven moderately insulin-resistant nondiabetic subjects. Interventions. Each subject was studied three times at 2–3 weeks intervals; metoprolol (5 mg), Enalaprilat (2 mg) or saline infusions were used. Methods. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy expenditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to Enalaprilat (2.1±0.2 vs. 2.8±0.4 mL per 100 mL min-1; P

Norman Paradise - One of the best experts on this subject based on the ideXlab platform.

  • Enalaprilat improves systemic and mesenteric blood flow during resuscitation from hemorrhagic shock in dogs.
    Shock, 2003
    Co-Authors: Piper L Wall, Charisse M Buising, Larhee Henderson, B. Freeman, R. Vincent, Jeffrey Albright, Norman Paradise
    Abstract:

    We investigated the systemic and mesenteric cardiovascular effects of administering Enalaprilat during resuscitation from hemorrhage. Dogs were hemorrhaged (mean arterial pressure [MAP] 40-45 mmHg for 30 min, then 30-35 mmHg for 30 min) and were then resuscitated with intermittent lactated Ringer's solution (200 mL/kg/h during first 40 min, and 60 mL/kg/h during the following 130 min, MAP 75-80 mmHg). A constant-rate infusion of saline with or without Enalaprilat (0.02 mg/kg/h) was initiated after 40 min of resuscitation. Blood flows declined with hemorrhage, increased with resuscitation, and then declined during the initial 40 min of resuscitation. Enalaprilat administration resulted in blood flow increases not seen in the controls (ending values for cardiac index: 2.8 +/- 0.4 L/min/m2 vs. 1.6 +/- 0.3 L/min/m2; celiac arterial flow 314 +/- 66 L/min/m2 vs. 139 +/- 13 mL/min/m2; and portal venous flow 596 +/- 172 L/min/m2 vs. 414 +/- 81 mL/min/m2 for Enalaprilat versus controls, respectively). The greater flows with Enalaprilat appeared to be due to prevention of the increases in afterload noted in the controls (ending arterial elastance values 3.73 +/- 0.97 mmHg/m2/mL vs. 7.74 +/- 1.80 mmHg/m2/mL for Enalaprilat versus controls, respectively). We conclude that administration of a constant-rate infusion of Enalaprilat during resuscitation can be used to improve systemic and mesenteric blood flow.

  • Enalaprilat improves systemic cardiovascular parameters and mesenteric blood flow during hypotensive resuscitation from hemorrhagic shock in dogs
    Shock, 2002
    Co-Authors: Piper L Wall, Charisse M Buising, Larhee Henderson, Tyler Rickers, Alberto Cardenas, Lisa Owens, Gregory Timberlake, Norman Paradise
    Abstract:

    Resuscitative interventions that improve mesenteric perfusion without causing instability in systemic arterial pressures may be helpful for improving trauma patient outcomes. Blocking angiotensin II formation with Enalaprilat may be such an intervention. Two questions were addressed in this two-part study investigating resuscitation from hemorrhagic shock in dogs: Can systemic arterial pressures be maintained while administering a constant rate infusion of Enalaprilat during resuscitation, and can Enalaprilat improve cardiovascular status during resuscitation? Animals were hemorrhaged to a mean arterial pressure (MAP) of 40 to 45 mmHg for 30 min and then 30 to 35 mmHg for 30 min. Group I (n = 5) was resuscitated to a MAP 60 to 65 mmHg with Enalaprilat (0.02 mg/kg/h). Group II was resuscitated to a MAP 40 to 45 mmHg with (n = 5) or without (n = 5) Enalaprilat. Resuscitation in both groups consisted of intermittent intravenous lactated Ringer's solution (60 mUkg/h) to reach and maintain the target MAPs. Systemic arterial pressures were unaffected by Enalaprilat during resuscitation in Group 1, allowing us to proceed to the second study. During severely hypotensive resuscitation (Group II), systemic arterial pressures were also stable and Enalaprilat administration was associated with increases (P ≤ 0.02) in cardiac index (+1.2 L/min/m 2 ), stroke volume index (SVI) (+14.5 mL/m 2 ), superior mesenteric artery flow (+80 mL/min), stroke work (+561 mmHg/mL/m 2 ), and left ventricular power output (+55.7 mmHg/L/min/m 2 ). Corresponding increases were not observed in controls. We conclude that administration of a constant rate infusion of Enalaprilat during resuscitation can be accomplished without causing a hypotensive crisis. Since Enalaprilat significantly improved cardiovascular status including mesenteric perfusion even during intentional hypotension, it has potential value for improving the treatment of trauma patients.

Earle Stellwagen - One of the best experts on this subject based on the ideXlab platform.

  • the sensitivity of the cis trans isomerization of enalapril and Enalaprilat to solvent conditions
    Journal of Pharmacy and Pharmacology, 2005
    Co-Authors: Robin Ledger, Earle Stellwagen
    Abstract:

    The cis- and trans-isomers of enalapril and Enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of Enalaprilat is only perturbed by the ionization of its amine group. Increasing the hydrophobicity of the analyte solvent, as reflected in its molar polarization, increases the Z (cis) content of enalapril and markedly decreases the kinetics for isomerization. Far UV circular dichroic measurements suggest that the increase in Z (cis) content of enalapril is due to protonation of its carboxylate group. Taken together, the in-vitro properties of enalapril and Enalaprilat suggest that the in-vivo transformation of the prodrug enalapril to the inhibitor Enalaprilat and its delivery to angiotensin-converting enzyme should not be significantly limited by cis/trans-isomerization.

  • The sensitivity of the cis/trans-isomerization of enalapril and Enalaprilat to solvent conditions.
    Journal of Pharmacy and Pharmacology, 2005
    Co-Authors: Robin Ledger, Earle Stellwagen
    Abstract:

    The cis- and trans-isomers of enalapril and Enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of Enalaprilat is only perturbed by the ionization of its amine group. Increasing the hydrophobicity of the analyte solvent, as reflected in its molar polarization, increases the Z (cis) content of enalapril and markedly decreases the kinetics for isomerization. Far UV circular dichroic measurements suggest that the increase in Z (cis) content of enalapril is due to protonation of its carboxylate group. Taken together, the in-vitro properties of enalapril and Enalaprilat suggest that the in-vivo transformation of the prodrug enalapril to the inhibitor Enalaprilat and its delivery to angiotensin-converting enzyme should not be significantly limited by cis/trans-isomerization.

Johan G Eriksson - One of the best experts on this subject based on the ideXlab platform.

  • acute administration of metoprolol and Enalaprilat reduces insulin stimulated thermogenesis and skin blood flow
    Journal of Internal Medicine, 1996
    Co-Authors: J A Tuominen, Johan G Eriksson, Veikko A Koivisto
    Abstract:

    Tuominen JA, Eriksson JG, Koivisto VA (Department of Medicine, Helsinki University Central Hospital, and National Institute of Public Health, Helsinki, Finland). Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow. J Intern Med 1996; 239: 399–406. Objective. To examine the acute effects of intravenous metoprolol and Enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Design. Randomized, single-blind, placebo-controlled trial. Setting. Helsinki University Central Hospital, Finland. Subjects. Seven moderately insulin-resistant nondiabetic subjects. Interventions. Each subject was studied three times at 2–3 weeks intervals; metoprolol (5 mg), Enalaprilat (2 mg) or saline infusions were used. Methods. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy expenditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to Enalaprilat (2.1±0.2 vs. 2.8±0.4 mL per 100 mL min-1; P<0.05). Glucose-plus-insulin-stimulated thermogenesis and total energy expenditure were reduced both by metoprolol (71 and 5.2%; P<0.05 in both) and Enalaprilat (59%, P= 0.06; and 7.6%, P<0.05) as compared to the control study. Skin blood flow (laser Doppler) increased by 100% (P<0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearm and whole-body glucose uptake was not influenced by metoprolol or Enalaprilat administration. Conclusions. (i) Both metoprolol and Enalaprilat inhibit glucose-plus-insulin-induced thermogenesis and a rise in skin blood flow. (ii) Metoprolol further reduces forearm blood flow compared to Enalaprilat. (iii) Neither drug has any acute effect on insulin sensitivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both for energy balance and thermoregulation during periods of hyperinsulinaemia in man.

  • Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow.
    Journal of Internal Medicine, 1996
    Co-Authors: J A Tuominen, Johan G Eriksson, Veikko A Koivisto
    Abstract:

    Tuominen JA, Eriksson JG, Koivisto VA (Department of Medicine, Helsinki University Central Hospital, and National Institute of Public Health, Helsinki, Finland). Acute administration of metoprolol and Enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow. J Intern Med 1996; 239: 399–406. Objective. To examine the acute effects of intravenous metoprolol and Enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. Design. Randomized, single-blind, placebo-controlled trial. Setting. Helsinki University Central Hospital, Finland. Subjects. Seven moderately insulin-resistant nondiabetic subjects. Interventions. Each subject was studied three times at 2–3 weeks intervals; metoprolol (5 mg), Enalaprilat (2 mg) or saline infusions were used. Methods. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy expenditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to Enalaprilat (2.1±0.2 vs. 2.8±0.4 mL per 100 mL min-1; P