MECHANISMS INVOLVED IN THE CARDIOVASCULAR-RENAL ACTIONS OF NITRIC-OXIDE INHIBITION

The roles of the sympathetic nervous system, angiotensin II, and arginine vasopressin in the cardiovascular-renal responses to nitric oxide synthesis inhibition were examined in eight conscious dogs equipped with arterial and venous catheters and a nonoccluding bladder catheter. Nitric oxide inhibition was achieved by intravenous infusion of N-G-nitro-L-arginine methyl ester (L-NAME) at 37.1 nmol/kg per minute for 140 minutes in the control group. The same dogs, after a 1-week recovery, were pretreated for 2 days with either prazosin for alpha(1) blockade, prazosin plus propranolol for alpha(1) plus beta blockade, L-158,809 for angiotensin receptor blockade, or d(CH2)Tyr(Me)arginine vasopressin for vasopressin-V-1 blockade, and the L-NAME infusion was repeated. After 140 minutes of L-NAME infusion into the control group, mean arterial pressure and renal vascular resistance had increased 16% and 71%, and renal blood flow, glomerular filtration rate, urine flow, and urinary sodium excretion had decreased 33%, 16%, 61%, and 64%, respectively. The decrement in renal blood flow and glomerular filtration during L-NAME administration was unaffected by any of the neurohumoral blockers. During V-1 blockade L-NAME resulted in only a 3% increase in arterial pressure, attenuation of the renal vascular resistance response, and almost total elimination of the decrease in urine flow. During angiotensin blockade the L-NAME-induced increase in arterial pressure was markedly attenuated, and the decrease in urinary sodium excretion was attenuated in the alpha(1) plus beta blockade group. In conclusion, short-term renal and cardiovascular effects of nitric oxide synthesis inhibition in conscious dogs may be mediated, in order of importance, by arginine vasopressin, angiotensin II, and the sympathetics.