The Experts below are selected from a list of 189 Experts worldwide ranked by ideXlab platform
Jorge L Pesquero - One of the best experts on this subject based on the ideXlab platform.
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pro renin receptor expression in myocardial infarction in transgenic mice expressing rat Tonin
International Journal of Biological Macromolecules, 2017Co-Authors: Amanda Aparecida Ribeiro, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, M C Irigoyen, Rebeca Padrao Amorim, Ivana C Moraessilva, Dulce Elena CasariniAbstract:Abstract The (pro)renin receptor [(P)RR] has been implicated as a renin/prorenin receptor, and plays a role in local renin angiotensin system activation. Our goal was to investigate whether a transgenic mouse that expresses rat Tonin [TGM‘(rTon)] can regulate (P)RR mRNA levels. Control (C) and TGM‘(rTon) animals were subdivided into the C sham, C MI, TGM‘(rTon) sham, and TGM‘(rTon) MI groups. The levels of Tonin, (P)RR, and renin were determined using RT-PCR mRNA. Tonin activity as determined by RIE was significantly increased in the TGM‘(rTon) sham group as compared to the C sham group in the atrium (AT) and right ventricle (RV), respectively. In most mice, Tonin mRNA levels were significantly reduced compared to those in the TGM‘(rTon) sham group in the atria. In this structure, the (P)RR mRNA levels were statistically significantly reduced in the TGM‘(rTon) sham and TGM‘(rTon) MI groups compared to the control groups. However, the (P)RR mRNA values were significantly increased when we compared the TGM‘(rTon) MI vs TGM‘(rTon) sham groups. In the RV, the renin mRNA levels in the TGM‘(rTon) sham group were significantly reduced compared to the C sham group. Tonin overexpression may act in the regulation of (P)RR mRNA levels during MI.
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characterization of the renal renin angiotensin system in transgenic mice that express rat Tonin
Journal of the Renin-Angiotensin-Aldosterone System, 2015Co-Authors: Amanda Aparecida Ribeiro, João Bosco Pesquero, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, Daniele Ferreira, M C Irigoyen, Dulce Elena CasariniAbstract:Introduction: Tonin is an enzyme that is able to generate angiotensin II (Ang II) from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to characterize the renal renin-angiotensin system in transgenic mice that express rat Tonin (TGM`(rTon)). Materials and methods: Mice were euthanized and the kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and angiotensin II- converting enzyme (ACE2) expression was analyzed by Western blotting. Results: Tonin activity was significantly increased in TGM`(rTon) compared to their respective wild-type (WT) littermates (1.7 ± 0.21 vs 0.11 ± 0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive correlation with Tonin expression in both TGM`(rTon) and their respective wild-type littermates. The ACE activity and expression levels of 65- kDa N-domain angiotensin I-converting enzyme isoform were significantly increased in the TGM`(rTon) when compared with WT. ACE2 expression levels were statistically significantly higher in the TGM`(rTon) when compared with WT. Angiotensin 1-7 (Ang(1-7)) and Ang I levels were significantly lower in the TGM`(rTon). Conclusions: We suggest that the environment of Tonin abundance may increase N-domain ACE activity liberated by a secretase able to cleave somatic ACE.
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cardiovascular and electrocardiographic parameters after Tonin administration in wistar rats
Regulatory Peptides, 2013Co-Authors: Denis D Damasceno, Mercia P Lima, Daisy Fonseca Motta, Anderson J Ferreira, Judson F Quintaojunior, Lucas Rios Drummond, Antonio Jose Natali, Alvair P Almeida, Jorge L PesqueroAbstract:In order to understand the mechanisms of interaction between Tonin-angiotensin and renin-angiotensin systems (RAS) we evaluated, "in vivo" and "in vitro", in Wistar rats, cardiovascular and electrocardiographic parameters after Tonin administration. Arterial pressure (AP) and electrocardiogram (ECG) were recorded in awake animals before and after Tonin administration. Langendorff technique was used to analyze cardiac function in isolated heart in the presence of Tonin and video motion edge detection system was used to evaluate the effect of Tonin upon contractile function of isolated rat ventricular cardiomyocytes. After Tonin infusion rats presented significantly higher diastolic and mean arterial pressure (MAP) and heart rate (HR) as compared with control. The ECG analysis revealed shorter RR interval, increase in the low-frequency (LF) range of the heart rate variability (HRV) power (%) and decrease in the high-frequency (HF) of HRV power (%). Isolated hearts perfused with Tonin presented an increase in the arterial coronary pressure (ACP) and decline in the ventricular systolic tension (ST), maximal (dT/dt+) and minimal (dT/dt) contractility. The rates of contraction and relaxation of isolated ventricular cardiomyocytes were significantly increased due to the presence of Tonin. The angiotensin II (Ang II) levels in the coronary sinus effluent increased in the presence of Tonin in a dose-dependent manner and the effect of Tonin upon ACP was completely blocked by candesartan. Tonin is able to generate the vasoconstrictor peptide Ang II in the isolated heart of the rat and the cardiovascular response induced by Tonin was completely blocked by candesartan, an indication that the action of Ang II on Ang II type 1 (AT1) receptors is the major mechanism of the heart effects. Tonin affects cardiomyocyte contractile function which may be due to interference with Ca(2+) handling.
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increased blood pressure and water intake in transgenic mice expressing rat Tonin in the brain
Biological Chemistry, 2010Co-Authors: Cibele C Cardoso, João Bosco Pesquero, Mercia P Lima, Anderson J Ferreira, Jorge L Pesquero, Natalia Alenina, Fatimunnisa Qadri, Volkmar Gross, Mihail Todiras, Michael BaderAbstract:Tonin is a serine proteinase of the kallikrein family able to produce angiotensin II directly from angiotensinogen. In order to clarify the importance of this enzyme for the central nervous control of the cardiovascular system, we have generated transgenic mice, TGM(rTon), which express rat Tonin in astrocytes. These mice present high levels of Tonin mRNA and activity specifically in the brain. As a consequence, TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. The AT(1) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) as compared to the wild type suggesting a release of the peptide from the brain into the circulation. However, AT(1) receptors are desensitized in this transgenic model as shown by a blunted pressor response to intravenous application of angiotensin II. In conclusion, Tonin in the brain may represent an alternative pathway to generate angiotensin II with effects on the cardiovascular system.
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Tonin in rat heart with experimental hypertrophy
American Journal of Physiology-heart and Circulatory Physiology, 2003Co-Authors: Julio Cesar Borges, Eliane S. L. Lomez, Ronaldo C. Araujo, Michael Bader, João Bosco Pesquero, J A Silva, Maria Aparecida Gomes, Katia Moraes Leite, Jorge L PesqueroAbstract:Tonin-specific activity in the atrium were 2.6- and 5.5-fold higher than those of the left and right ventricle, respectively. After treatment, the levels of Tonin-specific activity increased twofold in the atrium but did not change in the ventricles. Renin expression was not detectable in these structures, and ACE expression levels did not change with treatment. AG expression was detected in the left ventricle at very low levels compared with the atrium and increased significantly only in the hypertrophied atrium (1.8-fold). Tonin mRNA was not detected in the ventricle but was found at low levels in the atrium, which increased after isoproterenol treatment. Our results permit us to conclude that Tonin may play a role in the process of heart hypertrophy in the rat.
João Bosco Pesquero - One of the best experts on this subject based on the ideXlab platform.
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characterization of the renal renin angiotensin system in transgenic mice that express rat Tonin
Journal of the Renin-Angiotensin-Aldosterone System, 2015Co-Authors: Amanda Aparecida Ribeiro, João Bosco Pesquero, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, Daniele Ferreira, M C Irigoyen, Dulce Elena CasariniAbstract:Introduction: Tonin is an enzyme that is able to generate angiotensin II (Ang II) from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to characterize the renal renin-angiotensin system in transgenic mice that express rat Tonin (TGM`(rTon)). Materials and methods: Mice were euthanized and the kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and angiotensin II- converting enzyme (ACE2) expression was analyzed by Western blotting. Results: Tonin activity was significantly increased in TGM`(rTon) compared to their respective wild-type (WT) littermates (1.7 ± 0.21 vs 0.11 ± 0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive correlation with Tonin expression in both TGM`(rTon) and their respective wild-type littermates. The ACE activity and expression levels of 65- kDa N-domain angiotensin I-converting enzyme isoform were significantly increased in the TGM`(rTon) when compared with WT. ACE2 expression levels were statistically significantly higher in the TGM`(rTon) when compared with WT. Angiotensin 1-7 (Ang(1-7)) and Ang I levels were significantly lower in the TGM`(rTon). Conclusions: We suggest that the environment of Tonin abundance may increase N-domain ACE activity liberated by a secretase able to cleave somatic ACE.
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increased blood pressure and water intake in transgenic mice expressing rat Tonin in the brain
Biological Chemistry, 2010Co-Authors: Cibele C Cardoso, João Bosco Pesquero, Mercia P Lima, Anderson J Ferreira, Jorge L Pesquero, Natalia Alenina, Fatimunnisa Qadri, Volkmar Gross, Mihail Todiras, Michael BaderAbstract:Tonin is a serine proteinase of the kallikrein family able to produce angiotensin II directly from angiotensinogen. In order to clarify the importance of this enzyme for the central nervous control of the cardiovascular system, we have generated transgenic mice, TGM(rTon), which express rat Tonin in astrocytes. These mice present high levels of Tonin mRNA and activity specifically in the brain. As a consequence, TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. The AT(1) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) as compared to the wild type suggesting a release of the peptide from the brain into the circulation. However, AT(1) receptors are desensitized in this transgenic model as shown by a blunted pressor response to intravenous application of angiotensin II. In conclusion, Tonin in the brain may represent an alternative pathway to generate angiotensin II with effects on the cardiovascular system.
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Tonin in rat heart with experimental hypertrophy
American Journal of Physiology-heart and Circulatory Physiology, 2003Co-Authors: Julio Cesar Borges, Eliane S. L. Lomez, Ronaldo C. Araujo, Michael Bader, João Bosco Pesquero, J A Silva, Maria Aparecida Gomes, Katia Moraes Leite, Jorge L PesqueroAbstract:Tonin-specific activity in the atrium were 2.6- and 5.5-fold higher than those of the left and right ventricle, respectively. After treatment, the levels of Tonin-specific activity increased twofold in the atrium but did not change in the ventricles. Renin expression was not detectable in these structures, and ACE expression levels did not change with treatment. AG expression was detected in the left ventricle at very low levels compared with the atrium and increased significantly only in the hypertrophied atrium (1.8-fold). Tonin mRNA was not detected in the ventricle but was found at low levels in the atrium, which increased after isoproterenol treatment. Our results permit us to conclude that Tonin may play a role in the process of heart hypertrophy in the rat.
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Tonin expression in the rat brain and Tonin mediated central production of angiotensin ii
Physiology & Behavior, 2002Co-Authors: R C Araujo, Eliane S. L. Lomez, Michael Bader, João Bosco Pesquero, Mercia P Lima, Marie Sumitani, Jorge L PesqueroAbstract:Tonins are serine proteinases mainly found in the rat submandibular gland, which are capable of generating the pressor octapeptide angiotensin II (Ang II) not only from the classical substrate angiotensin I but also from the synthetic tetradecapeptide (AG(1-14)) and from angiotensinogen. In this work, Tonin expression levels were evaluated in astrocytes and brain areas of the rat. By two different techniques (ribonuclease protection assay and reverse transcription-polymerase chain reaction), we could verify the presence of Tonin mRNA in astrocytes and in the thalamus of the rat brain. Sequencing of the amplified brain cDNA determined it to be identical to that found in the submandibular gland. Central microinjection of Tonin produced a transient (10-20 min) elevation of blood pressure and heart rate and induced water and saline intake within the first 10 min after injection. Urinary volume and salt excretion increased within 7 h after Tonin injection. These effects were partially blocked by previously administered losartan, indicating that Tonin effectively induced a central Ang II formation. Our data suggest that Tonin may be an alternative pathway to Ang II generation in the brain and could participate in the physiological effects exerted by Ang II such as water and saline intake and blood pressure elevation.
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Tonin and Kallikrein in the Brain of Transgenic Rat Line Expressing Human Tissue Kallikrein
Hypertension, 2002Co-Authors: Eliane S. L. Lomez, Ronaldo C. Araujo, Michael Bader, João Bosco PesqueroAbstract:A transgenic rat line harboring the human tissue kallikrein gene was investigated for expression and activity of Tonin and kallikrein in different regions of the brain. The introduction of the transgene into the rat genome produced a significant augmentation of the expression levels and activity of rat tissue kallikrein. The possibility that human kallikrein does not hydrolyze the rat substrate is probably responsible for the augmented expression of the rat enzyme. On the other hand, although expression of Tonin was significantly reduced, Tonin activity was not altered in most brain structures, except for cerebellum and neurohypophysis.
Michael Bader - One of the best experts on this subject based on the ideXlab platform.
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increased blood pressure and water intake in transgenic mice expressing rat Tonin in the brain
Biological Chemistry, 2010Co-Authors: Cibele C Cardoso, João Bosco Pesquero, Mercia P Lima, Anderson J Ferreira, Jorge L Pesquero, Natalia Alenina, Fatimunnisa Qadri, Volkmar Gross, Mihail Todiras, Michael BaderAbstract:Tonin is a serine proteinase of the kallikrein family able to produce angiotensin II directly from angiotensinogen. In order to clarify the importance of this enzyme for the central nervous control of the cardiovascular system, we have generated transgenic mice, TGM(rTon), which express rat Tonin in astrocytes. These mice present high levels of Tonin mRNA and activity specifically in the brain. As a consequence, TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. The AT(1) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) as compared to the wild type suggesting a release of the peptide from the brain into the circulation. However, AT(1) receptors are desensitized in this transgenic model as shown by a blunted pressor response to intravenous application of angiotensin II. In conclusion, Tonin in the brain may represent an alternative pathway to generate angiotensin II with effects on the cardiovascular system.
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Tonin in rat heart with experimental hypertrophy
American Journal of Physiology-heart and Circulatory Physiology, 2003Co-Authors: Julio Cesar Borges, Eliane S. L. Lomez, Ronaldo C. Araujo, Michael Bader, João Bosco Pesquero, J A Silva, Maria Aparecida Gomes, Katia Moraes Leite, Jorge L PesqueroAbstract:Tonin-specific activity in the atrium were 2.6- and 5.5-fold higher than those of the left and right ventricle, respectively. After treatment, the levels of Tonin-specific activity increased twofold in the atrium but did not change in the ventricles. Renin expression was not detectable in these structures, and ACE expression levels did not change with treatment. AG expression was detected in the left ventricle at very low levels compared with the atrium and increased significantly only in the hypertrophied atrium (1.8-fold). Tonin mRNA was not detected in the ventricle but was found at low levels in the atrium, which increased after isoproterenol treatment. Our results permit us to conclude that Tonin may play a role in the process of heart hypertrophy in the rat.
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Tonin expression in the rat brain and Tonin mediated central production of angiotensin ii
Physiology & Behavior, 2002Co-Authors: R C Araujo, Eliane S. L. Lomez, Michael Bader, João Bosco Pesquero, Mercia P Lima, Marie Sumitani, Jorge L PesqueroAbstract:Tonins are serine proteinases mainly found in the rat submandibular gland, which are capable of generating the pressor octapeptide angiotensin II (Ang II) not only from the classical substrate angiotensin I but also from the synthetic tetradecapeptide (AG(1-14)) and from angiotensinogen. In this work, Tonin expression levels were evaluated in astrocytes and brain areas of the rat. By two different techniques (ribonuclease protection assay and reverse transcription-polymerase chain reaction), we could verify the presence of Tonin mRNA in astrocytes and in the thalamus of the rat brain. Sequencing of the amplified brain cDNA determined it to be identical to that found in the submandibular gland. Central microinjection of Tonin produced a transient (10-20 min) elevation of blood pressure and heart rate and induced water and saline intake within the first 10 min after injection. Urinary volume and salt excretion increased within 7 h after Tonin injection. These effects were partially blocked by previously administered losartan, indicating that Tonin effectively induced a central Ang II formation. Our data suggest that Tonin may be an alternative pathway to Ang II generation in the brain and could participate in the physiological effects exerted by Ang II such as water and saline intake and blood pressure elevation.
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Tonin and Kallikrein in the Brain of Transgenic Rat Line Expressing Human Tissue Kallikrein
Hypertension, 2002Co-Authors: Eliane S. L. Lomez, Ronaldo C. Araujo, Michael Bader, João Bosco PesqueroAbstract:A transgenic rat line harboring the human tissue kallikrein gene was investigated for expression and activity of Tonin and kallikrein in different regions of the brain. The introduction of the transgene into the rat genome produced a significant augmentation of the expression levels and activity of rat tissue kallikrein. The possibility that human kallikrein does not hydrolyze the rat substrate is probably responsible for the augmented expression of the rat enzyme. On the other hand, although expression of Tonin was significantly reduced, Tonin activity was not altered in most brain structures, except for cerebellum and neurohypophysis.
Mercia P Lima - One of the best experts on this subject based on the ideXlab platform.
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pro renin receptor expression in myocardial infarction in transgenic mice expressing rat Tonin
International Journal of Biological Macromolecules, 2017Co-Authors: Amanda Aparecida Ribeiro, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, M C Irigoyen, Rebeca Padrao Amorim, Ivana C Moraessilva, Dulce Elena CasariniAbstract:Abstract The (pro)renin receptor [(P)RR] has been implicated as a renin/prorenin receptor, and plays a role in local renin angiotensin system activation. Our goal was to investigate whether a transgenic mouse that expresses rat Tonin [TGM‘(rTon)] can regulate (P)RR mRNA levels. Control (C) and TGM‘(rTon) animals were subdivided into the C sham, C MI, TGM‘(rTon) sham, and TGM‘(rTon) MI groups. The levels of Tonin, (P)RR, and renin were determined using RT-PCR mRNA. Tonin activity as determined by RIE was significantly increased in the TGM‘(rTon) sham group as compared to the C sham group in the atrium (AT) and right ventricle (RV), respectively. In most mice, Tonin mRNA levels were significantly reduced compared to those in the TGM‘(rTon) sham group in the atria. In this structure, the (P)RR mRNA levels were statistically significantly reduced in the TGM‘(rTon) sham and TGM‘(rTon) MI groups compared to the control groups. However, the (P)RR mRNA values were significantly increased when we compared the TGM‘(rTon) MI vs TGM‘(rTon) sham groups. In the RV, the renin mRNA levels in the TGM‘(rTon) sham group were significantly reduced compared to the C sham group. Tonin overexpression may act in the regulation of (P)RR mRNA levels during MI.
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characterization of the renal renin angiotensin system in transgenic mice that express rat Tonin
Journal of the Renin-Angiotensin-Aldosterone System, 2015Co-Authors: Amanda Aparecida Ribeiro, João Bosco Pesquero, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, Daniele Ferreira, M C Irigoyen, Dulce Elena CasariniAbstract:Introduction: Tonin is an enzyme that is able to generate angiotensin II (Ang II) from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to characterize the renal renin-angiotensin system in transgenic mice that express rat Tonin (TGM`(rTon)). Materials and methods: Mice were euthanized and the kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and angiotensin II- converting enzyme (ACE2) expression was analyzed by Western blotting. Results: Tonin activity was significantly increased in TGM`(rTon) compared to their respective wild-type (WT) littermates (1.7 ± 0.21 vs 0.11 ± 0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive correlation with Tonin expression in both TGM`(rTon) and their respective wild-type littermates. The ACE activity and expression levels of 65- kDa N-domain angiotensin I-converting enzyme isoform were significantly increased in the TGM`(rTon) when compared with WT. ACE2 expression levels were statistically significantly higher in the TGM`(rTon) when compared with WT. Angiotensin 1-7 (Ang(1-7)) and Ang I levels were significantly lower in the TGM`(rTon). Conclusions: We suggest that the environment of Tonin abundance may increase N-domain ACE activity liberated by a secretase able to cleave somatic ACE.
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cardiovascular and electrocardiographic parameters after Tonin administration in wistar rats
Regulatory Peptides, 2013Co-Authors: Denis D Damasceno, Mercia P Lima, Daisy Fonseca Motta, Anderson J Ferreira, Judson F Quintaojunior, Lucas Rios Drummond, Antonio Jose Natali, Alvair P Almeida, Jorge L PesqueroAbstract:In order to understand the mechanisms of interaction between Tonin-angiotensin and renin-angiotensin systems (RAS) we evaluated, "in vivo" and "in vitro", in Wistar rats, cardiovascular and electrocardiographic parameters after Tonin administration. Arterial pressure (AP) and electrocardiogram (ECG) were recorded in awake animals before and after Tonin administration. Langendorff technique was used to analyze cardiac function in isolated heart in the presence of Tonin and video motion edge detection system was used to evaluate the effect of Tonin upon contractile function of isolated rat ventricular cardiomyocytes. After Tonin infusion rats presented significantly higher diastolic and mean arterial pressure (MAP) and heart rate (HR) as compared with control. The ECG analysis revealed shorter RR interval, increase in the low-frequency (LF) range of the heart rate variability (HRV) power (%) and decrease in the high-frequency (HF) of HRV power (%). Isolated hearts perfused with Tonin presented an increase in the arterial coronary pressure (ACP) and decline in the ventricular systolic tension (ST), maximal (dT/dt+) and minimal (dT/dt) contractility. The rates of contraction and relaxation of isolated ventricular cardiomyocytes were significantly increased due to the presence of Tonin. The angiotensin II (Ang II) levels in the coronary sinus effluent increased in the presence of Tonin in a dose-dependent manner and the effect of Tonin upon ACP was completely blocked by candesartan. Tonin is able to generate the vasoconstrictor peptide Ang II in the isolated heart of the rat and the cardiovascular response induced by Tonin was completely blocked by candesartan, an indication that the action of Ang II on Ang II type 1 (AT1) receptors is the major mechanism of the heart effects. Tonin affects cardiomyocyte contractile function which may be due to interference with Ca(2+) handling.
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increased blood pressure and water intake in transgenic mice expressing rat Tonin in the brain
Biological Chemistry, 2010Co-Authors: Cibele C Cardoso, João Bosco Pesquero, Mercia P Lima, Anderson J Ferreira, Jorge L Pesquero, Natalia Alenina, Fatimunnisa Qadri, Volkmar Gross, Mihail Todiras, Michael BaderAbstract:Tonin is a serine proteinase of the kallikrein family able to produce angiotensin II directly from angiotensinogen. In order to clarify the importance of this enzyme for the central nervous control of the cardiovascular system, we have generated transgenic mice, TGM(rTon), which express rat Tonin in astrocytes. These mice present high levels of Tonin mRNA and activity specifically in the brain. As a consequence, TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. The AT(1) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) as compared to the wild type suggesting a release of the peptide from the brain into the circulation. However, AT(1) receptors are desensitized in this transgenic model as shown by a blunted pressor response to intravenous application of angiotensin II. In conclusion, Tonin in the brain may represent an alternative pathway to generate angiotensin II with effects on the cardiovascular system.
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Tonin expression in the rat brain and Tonin mediated central production of angiotensin ii
Physiology & Behavior, 2002Co-Authors: R C Araujo, Eliane S. L. Lomez, Michael Bader, João Bosco Pesquero, Mercia P Lima, Marie Sumitani, Jorge L PesqueroAbstract:Tonins are serine proteinases mainly found in the rat submandibular gland, which are capable of generating the pressor octapeptide angiotensin II (Ang II) not only from the classical substrate angiotensin I but also from the synthetic tetradecapeptide (AG(1-14)) and from angiotensinogen. In this work, Tonin expression levels were evaluated in astrocytes and brain areas of the rat. By two different techniques (ribonuclease protection assay and reverse transcription-polymerase chain reaction), we could verify the presence of Tonin mRNA in astrocytes and in the thalamus of the rat brain. Sequencing of the amplified brain cDNA determined it to be identical to that found in the submandibular gland. Central microinjection of Tonin produced a transient (10-20 min) elevation of blood pressure and heart rate and induced water and saline intake within the first 10 min after injection. Urinary volume and salt excretion increased within 7 h after Tonin injection. These effects were partially blocked by previously administered losartan, indicating that Tonin effectively induced a central Ang II formation. Our data suggest that Tonin may be an alternative pathway to Ang II generation in the brain and could participate in the physiological effects exerted by Ang II such as water and saline intake and blood pressure elevation.
Dulce Elena Casarini - One of the best experts on this subject based on the ideXlab platform.
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pro renin receptor expression in myocardial infarction in transgenic mice expressing rat Tonin
International Journal of Biological Macromolecules, 2017Co-Authors: Amanda Aparecida Ribeiro, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, M C Irigoyen, Rebeca Padrao Amorim, Ivana C Moraessilva, Dulce Elena CasariniAbstract:Abstract The (pro)renin receptor [(P)RR] has been implicated as a renin/prorenin receptor, and plays a role in local renin angiotensin system activation. Our goal was to investigate whether a transgenic mouse that expresses rat Tonin [TGM‘(rTon)] can regulate (P)RR mRNA levels. Control (C) and TGM‘(rTon) animals were subdivided into the C sham, C MI, TGM‘(rTon) sham, and TGM‘(rTon) MI groups. The levels of Tonin, (P)RR, and renin were determined using RT-PCR mRNA. Tonin activity as determined by RIE was significantly increased in the TGM‘(rTon) sham group as compared to the C sham group in the atrium (AT) and right ventricle (RV), respectively. In most mice, Tonin mRNA levels were significantly reduced compared to those in the TGM‘(rTon) sham group in the atria. In this structure, the (P)RR mRNA levels were statistically significantly reduced in the TGM‘(rTon) sham and TGM‘(rTon) MI groups compared to the control groups. However, the (P)RR mRNA values were significantly increased when we compared the TGM‘(rTon) MI vs TGM‘(rTon) sham groups. In the RV, the renin mRNA levels in the TGM‘(rTon) sham group were significantly reduced compared to the C sham group. Tonin overexpression may act in the regulation of (P)RR mRNA levels during MI.
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characterization of the renal renin angiotensin system in transgenic mice that express rat Tonin
Journal of the Renin-Angiotensin-Aldosterone System, 2015Co-Authors: Amanda Aparecida Ribeiro, João Bosco Pesquero, Mercia P Lima, Jorge L Pesquero, Zaira Palomino, Leandro E Souza, Daniele Ferreira, M C Irigoyen, Dulce Elena CasariniAbstract:Introduction: Tonin is an enzyme that is able to generate angiotensin II (Ang II) from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to characterize the renal renin-angiotensin system in transgenic mice that express rat Tonin (TGM`(rTon)). Materials and methods: Mice were euthanized and the kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and angiotensin II- converting enzyme (ACE2) expression was analyzed by Western blotting. Results: Tonin activity was significantly increased in TGM`(rTon) compared to their respective wild-type (WT) littermates (1.7 ± 0.21 vs 0.11 ± 0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive correlation with Tonin expression in both TGM`(rTon) and their respective wild-type littermates. The ACE activity and expression levels of 65- kDa N-domain angiotensin I-converting enzyme isoform were significantly increased in the TGM`(rTon) when compared with WT. ACE2 expression levels were statistically significantly higher in the TGM`(rTon) when compared with WT. Angiotensin 1-7 (Ang(1-7)) and Ang I levels were significantly lower in the TGM`(rTon). Conclusions: We suggest that the environment of Tonin abundance may increase N-domain ACE activity liberated by a secretase able to cleave somatic ACE.