EFFECTS OF RENIN-ANGIOTENSIN BLOCKADE ON SYMPATHETIC REACTIVITY AND BETA-ADRENERGIC PATHWAY IN THE SPONTANEOUSLY HYPERTENSIVE RAT

As interactions between the renin-angiotensin and sympathetic nervous systems have been suggested in the pathogenesis of hypertension, we wa nted to investigate the effect of chronic renin-angiotensin blockade w ith losartan and enalaprilat on the sympathetic reactivity to hypotens ion and on the cardiac beta-adrenergic-coupled adenylyl cyclase pathwa y in 12-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensiv e rats (SHR). Both treatments, exerting equipotent shifts of angiotens in-pressure responses, lowered blood pressure and attenuated cardiac h ypertrophy similarly in SHR. The nitroprusside-induced hypotension was similar in both strains, but the associated increases in plasma catec holamines and heart rate were higher in SHR. In SHR treated with losar tan and enalaprilat, the nitroprusside-induced hypotension was greater and associated with markedly attenuated increases in norepinephrine a nd heart rate. The binding affinity of cardiac beta-adrenoceptors was significantly lower, and beta(2)-adrenoceptor subtype was dominant in untreated SHR in contrast to WKY, in which beta(1)-adrenoceptor subtyp e was dominant. Enalaprilat treatment increased total beta-adrenocepto r density, whereas both treatments restored the binding affinity and b eta(1)- and beta(2)-adrenoceptor proportions to normal in SHR. Isoprot erenol-, guanylylimidodiphosphate [Gpp(NH)p]-, and forskolin-stimulate d adenylyl cyclase reactivity was increased in SHR. Enalaprilat restor ed adenylyl cyclase reactivity to normal in SHR and reduced the sensit ivity (EC50) of Gpp(NH)p-induced cAMP formation in both strains, The p resent study supports the possibility that functional alterations of t he renin-angiotensin and sympathetic systems are involved in hypertens ion in SHR The antihypertensive action of losartan and enalaprilat in SHR may be partly mediated through the normalization of sympathetic hy perreactivity and the restoration of beta-adrenergic signaling pathway sensitivity.