Okuno T, Nagahama S, Lindheimer M D, Oparil S
Hypertension. 1983 Sep-Oct;5(5):653-62. doi: 10.1161/01.hyp.5.5.653.
Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 micrograms/0.5 microliter/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 +/- 3.3 compared to 181 +/- 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICV-injected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p less than 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control.
向成年自发性高血压大鼠（SHR）侧脑室（ICV）注入卡托普利可降低血压。本研究旨在探讨在高血压形成之前，脑内转换酶抑制对幼龄动物的影响，并确定卡托普利在多种可能导致该品系高血压发生的升压系统中所引起的变化。从7周龄开始，向雄性SHR的侧脑室注入卡托普利（1.25微克/0.5微升/小时）。四周后，收缩压仅为157±3.3，而注入赋形剂的对照组为181±3.9毫米汞柱，且脑室内注射血管紧张素I的升压作用减弱了50%。当静脉注入相同剂量的卡托普利时，高血压的发展与注入赋形剂的大鼠相同。与脑室内注入赋形剂组相比，脑室内注入卡托普利组的血清血管紧张素转换酶活性（SACE）和血浆精氨酸加压素（AVP）浓度显著升高（分别为p<0.001和0.05），而两组的血浆醛固酮浓度、肾素活性、液体摄入量、尿量和尿钠排泄量相似。卡托普利治疗对静息状态下评估的外周交感神经系统活性无影响。此外，脑室内注入卡托普利对端脑、间脑、中脑和脑桥延髓的AVP含量无影响。脑室内注入卡托普利治疗的动物端脑肾素活性升高，但在所检查的其他脑区未发生改变。这些数据表明，脑室内注入卡托普利可通过明显独立于液体和钠平衡及交感肾上腺系统改变的机制，减弱幼龄SHR高血压的发展。对血压的影响发生时，血浆或那些最常与血压控制相关的脑区的肾素活性或AVP含量并无变化。
