Baroreflex improvement in shr after ace inhibition involves angiotensin-(1-7).

ACE inhibitors are extensively used in the treatment of hypertension mainly because of their efficiency in reducing blood pressure levels and decreasing vascular and cardiac hypertrophy. In addition, ACE inhibitors improve baroreceptor reflex control. Chronic inhibition of ACE produces (in addition to decreased angiotensin II levels) a severe increase in angiotensin-(1-7) [Ang-(1-7)] levels in several species. We have previously shown that Ang-(1-7) produces a facilitation of the baroreflex control of heart rate. In this study, we evaluated the participation of endogenous Ang-(1-7) in the improvement of baroreflex sensitivity in spontaneously hypertensive rats after central infusion of ramiprilat, an ACE inhibitor. Reflex changes in heart rate were elicited, in conscious rats, by bolus injections of phenylephrine (baroreflex bradycardia) before and after intracerebroventricular infusion of (1) saline (8 microL/h), 4 hours (n=5); (2) ramiprilat (14 microg/h), 4 hours (n=6); (3) ramiprilat for 2 hours, followed by ramiprilat combined with A-779 (4 microg/h), a selective Ang-(1-7) antagonist, for an additional 2 hours (n=6); and (4) A-779 for 2 hours, followed by A-779 combined with ramiprilat for an additional 2 hours (n=5). Intracerebroventricular infusion of ramiprilat produced an important increase ( approximately 40%) in baroreflex sensitivity (evaluated as the ratio between changes in heart rate and changes in mean arterial pressure) that was completely reversed by A-779. Furthermore, intracerebroventricular infusion of A-779 prevented the improvement of the baroreflex sensitivity produced by ramiprilat. Intracerebroventricular infusion of saline or A-779 alone did not significantly alter the baroreflex sensitivity. These results suggest that endogenous Ang-(1-7) is involved in the improvement of baroreflex sensitivity observed in spontaneously hypertensive rats during central ACE inhibition.

Regulation of the kinin receptors after induction of myocardial infarction: a mini-review.

It is well known that the responses to vasoactive kinin peptides are mediated through the activation of two receptors termed bradykinin receptor B1 (B1R) and B2 (B2R). The physiologically prominent B2R subtype has certainly been the subject of more intensive efforts in structure-function studies and physiological investigations. However, the B1R activated by a class of kinin metabolites has emerged as an important subject of investigation within the study of the kallikrein-kinin system (KKS). Its inducible character under stress and tissue injury is therefore a field of major interest. Although the KKS has been associated with cardiovascular regulation since its discovery at the beginning of the last century, less is known about the B1R and B2R regulation in cardiovascular diseases like hypertension, myocardial infarction (MI) and their complications. This mini-review will summarize our findings on B1R and B2R regulation after induction of MI using a rat model. We will develop the hypothesis that differences in the expression of these receptors may be associated with a dual pathway of the KKS in the complex mechanisms of myocardial remodeling.

Regulation of the kinin receptors after induction of myocardial infarction: a mini-review

It is well known that the responses to vasoactive kinin peptides are mediated through the activation of two receptors termed bradykinin receptor B1 (B1R) and B2 (B2R). The physiologically prominent B2R subtype has certainly been the subject of more intensive efforts in structure-function studies and physiological investigations. However, the B1R activated by a class of kinin metabolites has emerged as an important subject of investigation within the study of the kallikrein-kinin system (KKS). Its inducible character under stress and tissue injury is therefore a field of major interest. Although the KKS has been associated with cardiovascular regulation since its discovery at the beginning of the last century, less is known about the B1R and B2R regulation in cardiovascular diseases like hypertension, myocardial infarction (MI) and their complications. This mini-review will summarize our findings on B1R and B2R regulation after induction of MI using a rat model. We will develop the hypothesis that differences in the expression of these receptors may be associated with a dual pathway of the KKS in the complex mechanisms of myocardial remodeling.

Altered heart rate and blood pressure variability in mice lacking the Mas protooncogene.

Heart rate variability is a relevant predictor of cardiovascular risk in humans. A significant genetic influence on heart rate variability is suggested, although the genes involved are ill-defined. The Mas-protooncogene encodes a G-protein-coupled receptor with seven transmembrane domains highly expressed in testis and brain. Since this receptor is supposed to interact with the signaling of angiotensin II, which is an important regulator of cardiovascular homeostasis, heart rate and blood pressure were analyzed in Mas-deficient mice. Using a femoral catheter the blood pressure of mice was measured for a period of 30 min and 250 data values per second were recorded. The mean values and range of heart rate and blood pressure were then calculated. Neither heart rate nor blood pressure were significantly different between knockout mice and controls. However, high resolution recording of these parameters and analysis of the data by non-linear dynamics revealed significant alterations in cardiovascular variability in Mas-deficient animals. In particular, females showed a strong reduction of heart rate variability. Furthermore, the data showed an increased sympathetic tone in knockout animals of both genders. The marked alterations detected in Mas-deficient mice of both genders suggest that the Mas-protooncogene is an important determinant of heart rate and blood pressure variability.