EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITION ON REGIONAL CEREBRAL BLOOD-FLOW AND VASCULAR-RESISTANCE IN CONSCIOUS AND ISOFLURANE-ANESTHETIZED RATS

Nitric oxide is an important regulator of the regional cerebral vascul ar tone. We compared the magnitude of nitric oxide-related changes in the vascular tone by studying the regional cerebral blood flow (rCBF) and vascular resistance in conscious and isoflurane-anesthetized rats by using a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine meth yl ester (L-NAME). In the conscious group-(n = 12), after cannulation of a femoral artery and two veins under isoflurane anesthesia, rats we re allowed to remain awake for 90 min. In the anesthetized group (n = 18), rats were anesthetized with 2% isoflurane and mechanically ventil ated. Six rats in each group were treated with L-NAME (2 mg.kg-1.min-1 for 30 min) or saline. For the remaining rats in the isoflurane-anest hetized group (n = 6), arterial blood pressure was increased by phenyl ephrine infusion to the same level as that in the L-NAME-treated, isof lurane-anesthetized rats. Regional vascular resistance was determined by the ratio of mean arterial blood pressure and rCBF which was measur ed by [C-14]iodoantipyrine. L-NAME significantly increased mean arteri al blood pressure in both the conscious (123 to 158 mm Hg) and anesthe tized (82 to 144 mm Hg) rats. Regional vascular resistance increased s ignificantly in all 12 brain regions studied with the average value in creasing from 1.19 +/- 0.33 mm Hg. mL-1.min.100 g to 2.22 +/- 0.48 (P < 0.0001) in the conscious and from 0.78 +/- 0.27 to 1.61 +/- 0.48 (P < 0.0001) in the isoflurane-anesthetized rats. L-NAME significantly de creased rCBF in the conscious animals. In the isoflurane-anesthetized rats, L-NAME significantly decreased CBF only in the medulla and pons, and phenylephrine infusion significantly increased rCBF in most of th e brain regions. Our study suggests that nitric oxide plays an importa nt role in regulating cerebral vascular tone in conscious as well as i n isoflurane-anesthetized rats.