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(Hypertension. 2001;37:1309.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Baroreflex Improvement in SHR After ACE Inhibition Involves Angiotensin-(1-7)

Silvia Heringer-Walther; Érica N. Batista; Thomas Walther; Mahesh C. Khosla; Robson A. S. Santos; Maria J. Campagnole-Santos

From the Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte (S.H.-W., E.N.B., R.A.S.S., M.J.C.-S.), Brazil; the Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Free University of Berlin (S.H.-W., T.W.), Berlin, Germany; and the Department of Neurosciences, Cleveland Clinic Foundation (M.C.K.), Cleveland, Ohio.

Correspondence to Maria Jose Campagnole-Santos, PhD, Departamento de Fisiologia e Biofísica, Av. Antonio Carlos, 6627-ICB-UFMG, 31270-901 Belo Horizonte, MG, Brazil. E-mail mjcs{at}icb.ufmg.br

Abstract—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 µL/h), 4 hours (n=5); (2) ramiprilat (14 µg/h), 4 hours (n=6); (3) ramiprilat for 2 hours, followed by ramiprilat combined with A-779 (4 µg/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 (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.

Key Words: angiotensin-(1-7) • baroreceptors • angiotensin-converting enzyme inhibitors • renin-angiotensin system • rats, inbred SHR • A-779

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