Attenuation of the development of spontaneous hypertension in rats by chronic central administration of captopril.

Abstract

SUMMARY 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 /u.g/0.5 /xl/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 ICVinjected 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 < 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. (Hypertension 5: 653-662, 1983) KEY WORDS • captopril • chronic central infusion • blood pressure • spontaneously hypertensive rats * renin-angiotensin-aldosterone system • catecholamines vasopressin

The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes

“…These results are consistent with previous reports that blockade of the formation or action of central AII does not alter baseline BP in normotensive rats. 20,21,37 To examine the possibility that the exaggerated activation of central AT-1 receptors in RAϩ mice results in altered sympathetic nerve and/or AVP outflow from the CNS, we determined the relative contribution of each of these pressor systems to BP in double-transgenic mice and controls. The finding that the depressor response to the V 1 antagonist was significantly greater in RAϩ mice compared with controls suggests an enhanced contribution of circulating AVP to vascular tone in this model.…”

“…For example, acute or chronic ICV administration of AII receptor antagonists markedly reduced BP in the adult spontaneously hypertensive rat (SHR), 12,20 and chronic ICV-converting enzyme inhibitor prevented the development of hypertension in young SHRs. 21 Indeed, compared with normotensive WistarKyoto rats, SHRs have elevated levels of brain RAS components 51,52 but normal plasma AII levels. Moreover, direct microinjection of losartan into the anterior hypothalamic area, an intrinsic brain site rich in AT-1 receptors with projections to PVN and SON, caused depressor responses in SHR but not WKY, 37 suggesting a role for endogenous AII at this intrinsic brain site in SHR.…”

Blockade of angiotensin AT1-receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats reduces blood pressure and sympathetic nerve discharge

“…Central administration of inhibitors of brain Ang II formation or action result in decreases in BP, [11][12][13][14] although these findings are not universal. 15 The mechanism(s) by which brain Ang II might be involved in hypertension are still being elucidated.…”

Effects of brain renin- angiotensin system inhibition in ISIAH rats with inherited stress-induced arterial hypertension

“…в искусственной спинно-мозговой жидкости в количестве 250 мкг/кг веса животного в день. Дозировка лозартана выбрана в соответствии с результатами работ (Kishi et al, 2015); беназеприла -рассчитана как эквимолярная по отношению к известной эффективной концентрации его аналога каптоприла (Okuno et al, 1983). Срок хрониче-ского введения препаратов составил 13 дней.…”