Affiliation:
1. From the Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Abstract
Abstract
In this study, we evaluated the effect produced by lateral ventricle (intracerebroventricular, ICV) infusion of the selective angiotensin (Ang)-(1-7) antagonist,
d
-Ala
7
-Ang-(1-7) (A-779), in the modulation of the baroreflex control of heart rate in two-kidney, one clip renovascular hypertensive rats (2K1C) treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril. Twenty days after the surgery to produce renovascular hypertension, ICV cannulas were implanted in the rats with blood pressure (BP) greater than 145 mm Hg (n=33) and in sham-operated rats (n=32). Five days later, the rats were treated with enalapril (10 mg · kg
−1
· d
−1
; 6 days, in the drinking water) or vehicle (tap water). On the sixth day of treatment, direct continuous BP recording and measurement of reflex changes in heart rate elicited by phenylephrine were made in conscious rats before and at 1 hour of ICV infusion of saline (8 μL/h) or A-779 (4 μg/h). To evaluate the degree of ACE blockade produced by enalapril treatment, the pressor effect of Ang I (50 ng, IV, and 100 ng, ICV) and plasma ACE activity was determined. As expected, enalapril treatment in 2K1C produced a significant fall in BP, significant attenuation in the pressor response of Ang I (IV), and a reduction in plasma ACE activity. In addition, enalapril treatment increased the baroreflex sensitivity (0.76±0.04 versus 0.43±0.04 ms/mm Hg in 2K1C untreated rats). ICV infusion of A-779 reverted the improvement in baroreflex sensitivity produced by enalapril treatment in 2K1C (from 0.80±0.07 to 0.42±0.08 ms/mm Hg) and also attenuated the baroreflex sensitivity in untreated 2K1C (0.36±0.05 versus 0.48±0.06 ms/mm Hg) and untreated sham-operated rats (1.21±0.05 versus 0.78±0.17 ms/mm Hg). These results suggest that central endogenous Ang-(1-7) is involved at least in part in the improvement of baroreflex sensitivity observed in 2K1C after peripheral chronic ACE inhibition.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
86 articles.
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