ANGIOTENSIN-II - NITRIC-OXIDE INTERACTION AND THE DISTRIBUTION OF BLOOD-FLOW

Nitric oxide (NO) contributes to the regulation of regional blood flow . Inhibition of NO synthesis increases blood pressure and vascular res istance. Using radioactive microspheres and the substrate antagonist N (omega)-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) to block NO synthesis, we tested the hypothesis that there is a significant intera ction between the vasodilator NO and the vasoconstrictor angiotensin I I, which regulates regional hemodynamics. Further, we investigated the influence of anesthesia on this interaction. L-NAME increased blood p ressure, decreased cardiac output, and increased total peripheral resi stance in both anesthetized and conscious rats. In anesthetized rats, L-NAME decreased blood flow to visceral organs (i.e. kidney, intestine , and lung) but had little effect on blood flow to the brain, heart, o r hindlimb. Treating anesthetized rats with the angiotensin II recepto r antagonist losartan (10 mg/kg) attenuated the decrease in cardiac ou tput and the increase in total peripheral resistance without affecting the pressor response to L-NAME. Losartan also attenuated the visceral hemodynamic responses to L-NAME. In conscious rats, L-NAME decreased blood flow to all organ beds. Treating these rats with losartan only m arginally attenuated the increase in total peripheral resistance to L- NAME without significantly affecting the pressor response or the decre ase in cardiac output. Losartan had no effect on the regional hemodyna mic responses to L-NAME. These data suggest that NO-mediated vascular relaxation is an important regulator of total peripheral and organ vas cular resistance. Anesthesia appears to decrease the influence of NO o n organ perfusion, diminishing its effect on the cerebral cardiac and peripheral circulation, while amplifying its apparent interaction with angiotensin in the visceral vasculature.