Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade-induced hypertension.

Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1-adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1-adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO-blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1-adrenoceptor and AT1 stimulation.