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(Hypertension. 1997;30:278-287.)
© 1997 American Heart Association, Inc.

Articles

Effects of Renin-Angiotensin Blockade on Sympathetic Reactivity and ß-Adrenergic Pathway in the Spontaneously Hypertensive Rat

Annik K. Laflamme; Laurence Oster; René Cardinal; ; Jacques de Champlain

From Groupe de Recherche sur le Système Nerveux Autonome, Département de Pharmacologie (A.K.-L., R.C.) et Département de Physiologie (L.O., J. de C.), Faculté de Médecine, Université de Montréal (Québec, Canada).

Correspondence to Dr Jacques de Champlain, Département de Physiologie, Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada, H3C 3J7. E-mail laflaman{at}ere.umontreal.ca

Abstract As interactions between the renin-angiotensin and sympathetic nervous systems have been suggested in the pathogenesis of hypertension, we wanted to investigate the effect of chronic renin-angiotensin blockade with losartan and enalaprilat on the sympathetic reactivity to hypotension and on the cardiac ß-adrenergic–coupled adenylyl cyclase pathway in 12-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Both treatments, exerting equipotent shifts of angiotensin-pressure responses, lowered blood pressure and attenuated cardiac hypertrophy similarly in SHR. The nitroprusside-induced hypotension was similar in both strains, but the associated increases in plasma catecholamines and heart rate were higher in SHR. In SHR treated with losartan and enalaprilat, the nitroprusside-induced hypotension was greater and associated with markedly attenuated increases in norepinephrine and heart rate. The binding affinity of cardiac ß-adrenoceptors was significantly lower, and ß₂-adrenoceptor subtype was dominant in untreated SHR in contrast to WKY, in which ß₁-adrenoceptor subtype was dominant. Enalaprilat treatment increased total ß-adrenoceptor density, whereas both treatments restored the binding affinity and ß₁- and ß₂-adrenoceptor proportions to normal in SHR. Isoproterenol-, guanylylimidodiphosphate [Gpp(NH)p]–, and forskolin-stimulated adenylyl cyclase reactivity was increased in SHR. Enalaprilat restored adenylyl cyclase reactivity to normal in SHR and reduced the sensitivity (EC₅₀) of Gpp(NH)p-induced cAMP formation in both strains. The present study supports the possibility that functional alterations of the renin-angiotensin and sympathetic systems are involved in hypertension in SHR. The antihypertensive action of losartan and enalaprilat in SHR may be partly mediated through the normalization of sympathetic hyperreactivity and the restoration of ß-adrenergic signaling pathway sensitivity.

Key Words: hypertension, genetic • autonomic nervous system • renin-angiotensin system • receptors, adrenergic, beta • adenylyl cyclase • losartan • enalaprilat

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