ANGIOTENSIN-II AND ALPHA(1)-ADRENERGIC TONE IN CHRONIC NITRIC-OXIDE BLOCKADE-INDUCED HYPERTENSION

Nitric oxide (NO) is a tonically produced vasodilator that maintains b lood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibi tor nitro-L-arginine methyl ester (L-NAME), which produced sustained h ypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT(1)) receptor wi th losartan had little effect on BP and RVR in either chronically NO-b locked or normal conscious rats. Acute blockade of the alpha(1)-adreno ceptor with prazosin produced moderate similar falls in BP in both chr onically NO-blocked and normal rats. The combination of AT(1) and alph a(1)-adrenoceptor blockade was profoundly antihypertensive and was par ticularly effective in lowering BP in chronically NO-blocked rats wher e the hypertension was obliterated. In contrast, the increased RVR per sisted in chronically NO-blocked rats receiving combined acute AT(1) a nd alpha(1)-adrenoceptor blockade. These observations indicate that, i n the sustained phase of chronic NO blockade, the hypertension is larg ely due to the combined activities of alpha(1)-adrenoceptor and AT(1) stimulation.