Duration of the hemodynamic effects of N-G-nitro-L-arginine methyl ester in vivo

The objective of this study was to quantify the duration of the hemodynamic activity of N-G-nitro-L-arginine methyl eater (L-NAME) in a variety of dif ferent tissues following a single bolus injection of this nitric oxide synt hase inhibitor to healthy rats. L-NAME (15 mu mol.kg(-1)) was injected (ip) into rats to produce maximal inhibition of endothelial cell NOS. Animals w ere subsequently anesthetized and blood flow was quantified using the radio active microsphere/reference organ technique. At 1 h following a single bol us injection of L-NAME blood flow was reduced to the entire gastrointestina l tract, pancreas, and liver. Three hours following L-NAME administration, blood flow to the stomach and upper small intestine had returned to pretrea tment levels; however, blood flow to the jejunum, ileal-jejunal junction, a nd colon remained significantly reduced. Splenic blood flow was significant ly reduced and hepatic arterial blood flow was further reduced at this time as well. After 6 h following L-NAME administration, blood flow in all orga ns had completely recovered to control levels. Although cardiac index and t otal peripheral resistance had also returned to preinjection values at this time, mean arterial pressure remained elevated at 6 h posttreatment. Blood flow to the brain, lungs, and psoas muscle were unaffected by L-NAME admin istration at any time point. Taken together, these data demonstrate a diffe rential regulation of vascular tone by NO in different vascular beds and, d epending upon the organ system in question, the vasoactive activity of L-NA ME may last from 3 to 6 h following a single bolus injection of this NOS in hibitor. (C) 2000 Academic Press.