FUNCTIONAL TOLERANCE TO ALPHA-ADRENERGIC RECEPTOR BLOCKADE IN THE SPONTANEOUSLY HYPERTENSIVE RAT HIGHLIGHTS THE MULTIFUNCTIONAL ROLE OF VASCULAR ANGIOTENSIN-II IN THE DEVELOPMENT OF HYPERTENSION

Treatment of spontaneously hypertensive rats (SHR) with ct-adrenocepto r antagonists failed to alter the development of hypertension in this animal model. However, agents such as captopril (CAP) and losartan (LO S) which interfere with the renin-angiotensin system effectively preve nted the development of hypertension. When tolerance occurred in the p resence of doxazosin (DOX) or phenoxybenzamine, there was an enhanced sensitivity to the blood pressure lowering influence of LOS. In the pr esence of CAP, at a dose that did not retard the development of blood pressure in the SHR, DOX treatment significantly offset the developmen t of hypertension in this strain. These results suggest that a functio nal tolerance to agents that interfere with the sympathetic nervous sy stem is mediated by the renin-angiotensin system. Angiotensin-converti ng enzyme inhibition was associated with a normalization of the enhanc ed contraction of the mesenteric vascular bed seen in preparations fro m the SHR and a suppression in the development of the vascular amplifi er. The results suggest that the sympathetic nervous system is unable to maintain an elevated blood pressure in the SHR during interference with the functioning of the renin-angiotensin system. Conversely, unde r conditions of a-adrenoceptor blockade, angiotensin II can maintain a n elevated blood pressure in the SHR.