Vascular wall renin in spontaneously hypertensive rats. Potential relevance to hypertension maintenance and antihypertensive effect of captopril.

Abstract

SUMMARY Relationships among systolic blood pressure (SBP), plasma renin activity (PRA), arterial renin concentrations (ARC), and venous renin concentrations (VRC) were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats before and after treatment with captopril. The ARC was elevated in SHR relative to WKY whereas VRC was not. Similarly, ARC was related to SBP (/• = 0.69, p < 0.01) whereas PRA was not (r = 0.04). Captopril (100 mg/kg daily by mouth for 8 days) decreased blood pressure significantly in both SHR and WKY. PRA as well as ARC and VRC were all increased by captopril. Bilateral nephrectomy virtually eliminated PRA but ARC was not significantly reduced over a 24-hour period. Bilateral nephrectomy also markedly attenuated the acute antihypertensive effects of captopril in SHR; however, a modest effect was still apparent. It is suggested that ARC in SHR, being higher than in WKY, may play a role in the genesis or maintenance of hypertension in this model. Furthermore, the effects of captopril in both intact and nephrectomized SHR may be related to the ability of captopril to inhibit the vascular formation of angiotensin II. Finally, vascular renin is probably not renal in origin and responds to typical feedback inhibition as unmasked by captopril administration. high plasma renin activity (PRA) such as acute twokidney renal hypertension, agents that interfere with the formation of, or receptor activation by, angiotensin II (All) are very effective in reducing blood pressure. Thus, renin inhibitors, ]~2 angiotensin-converting enzyme (ACE) inhibitors, 3 "* and All antagonists 9 have all been shown to either prevent the development of twokidney renal hypertension or reduce blood pressure shortly after the development of this form of hypertension. In chronic two-kidney one clip hypertension as well as one-kidney one clip and genetic hypertension, however, the relationship between PRA in the maintenance of hypertension and the antihypertensive effectiveness of inhibitors of the renin-angiotensin system is no longer clear. Thus, All antibodies and receptor antagonists do not substantially reduce blood pressure in chronic one-or two-kidney one clip hypertension or in spontaneously hypertensive rats (SHR) which are models that have normal or low PRA.

Angiotensin II Generation in Mesenteric Arteries in Rats: Effects of Nephrectomy, Deoxycorticosterone and Dexamethasone.

“…In fact, an increased aortic renin-like activity in the presence of a normal or decreased circulating renin level is reported in spontaneously hypertensive rats (Assad and Antonaccio, 1982) and the chronic phase of Goldblatt twokidney hypertension rats (Garst et al, 1979). This dissociation of the local and circulating RAS suggests that the local RAS may contribute little to the circulating RAS level.…”

Angiotensin II induces c-fos expression in smooth muscle via transcriptional control.

“…5 Recently, all of the components of the renin-angiotensin system have been demonstrated in the vessel wall, 29 - 30 and in some experimental models of hypertension (e.g., the spontaneously hypertensive rat and the chronic two-kidney, one clip hypertensive model) there is evidence to suggest that this local tissue renin-angiotensin system is elevated in hypertension. 31 - 32 This raises the possibility that an autocrine or paracrine system exists, which may be activated in hypertension. The link between this system and vascular hypertrophy in hypertension is an important subject of future research.…”

Brain angiotensin II and baroreceptor reflex function in spontaneously hypertensive rats.

“…The number of cages for each group is shown in parentheses and the number of rats in each of the four groups were 11, 11, 16, Antonaccio 26 and Unger et al 27 Chronic oral antihypertensive treatment of SHR and stroke prone SHR (SHRSP) with captopril increased renin concentrations in the wall of the aorta and in certain parts of the brain, and this elevation could be disassociated with increased plasma renin of renal origin. Direct evidence subsequently presented for inhibition of converting enzyme in brain after oral therapy was provided by Cohen and Kurz.…”