Britto R R, Santos R A, Fagundes-Moura C R, Khosla M C, Campagnole-Santos M J
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Hypertension. 1997 Sep;30(3 Pt 2):549-56. doi: 10.1161/01.hyp.30.3.549.
In this study, we evaluated the effect produced by lateral ventricle (intracerebroventricular, I.C.V.) infusion of the selective angiotensin (Ang)-(1-7) antagonist, D-Ala7-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, I.C.V. 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 x kg(-1) x 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 I.C.V. infusion of saline (8 microL/h) or A-779 (4 microg/h). To evaluate the degree of ACE blockade produced by enalapril treatment, the pressor effect of Ang I (50 ng, I.V., and 100 ng, I.C.V.) 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 (I.V.), 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). I.C.V. 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.
在本研究中，我们评估了在接受血管紧张素转换酶（ACE）抑制剂依那普利治疗的两肾一夹肾血管性高血压大鼠（2K1C）中，侧脑室（脑室内，I.C.V.）注入选择性血管紧张素（Ang）-(1-7)拮抗剂D-Ala7-Ang-(1-7)（A-779）对心率压力反射控制调节的影响。在造成肾血管性高血压的手术20天后，将I.C.V.套管植入血压（BP）大于145 mmHg的大鼠（n = 33）和假手术大鼠（n = 32）体内。五天后，大鼠接受依那普利（10 mg x kg(-1) x d(-1)；6天，饮水中给药）或赋形剂（自来水）治疗。在治疗的第六天，在清醒大鼠中，于I.C.V.注入生理盐水（8 μL/h）或A-779（4 μg/h）之前及注入1小时后，直接连续记录血压，并测量去氧肾上腺素引起的心率反射变化。为评估依那普利治疗产生的ACE阻断程度，测定了Ang I（50 ng，静脉注射，100 ng，脑室内注射）的升压作用及血浆ACE活性。如预期的那样，2K1C大鼠接受依那普利治疗后，血压显著下降，Ang I（静脉注射）的升压反应显著减弱，血浆ACE活性降低。此外，依那普利治疗增加了压力反射敏感性（2K1C未治疗大鼠为0.76±0.04对0.43±0.04 ms/mm Hg）。I.C.V.注入A-779使2K1C大鼠中依那普利治疗所产生的压力反射敏感性改善逆转（从0.80±0.07降至0.42±0.08 ms/mm Hg），并且减弱了未治疗的2K1C大鼠（0.36±0.05对0.48±0.06 ms/mm Hg）和未治疗的假手术大鼠（从1.21±0.05降至0.78±0.17 ms/mm Hg）的压力反射敏感性。这些结果表明，中枢内源性Ang-(1-7)至少部分参与了2K1C大鼠外周慢性ACE抑制后观察到压力反射敏感性的改善。
