INFLUENCE OF ENDOTHELIAL NITRIC-OXIDE ON ADRENERGIC CONTRACTILE RESPONSES OF HUMAN CEREBRAL-ARTERIES

The present study was designed to investigate the influence of the end othelium and that of the L-arginine pathway on the contractile respons es of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3-8 h before. EFS (1-8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10(-6) M). The inc reases in tension were of greater magnitude in arteries denuded of end othelium. N-G-monomethyl L-arginine (L-NMMA 10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but did n ot influence responses of endothelium-denuded arteries. L-arginine (10 (-4) M) reversed the potentiating effects of L-NMMA on EFS-induced con tractions. Norepinephrine induced concentration-dependent contractions , which were similar in arteries with and without endothelium or in ar teries treated with L-NMMA. Indomethacin (3 x 10(-6) M) had no signifi cant effect on the contractile response to EFS or on the inhibition by L-NMMA of acetylcholine-induced relaxation. These results suggest tha t the contractile response of human cerebral arteries to EFS is modula ted by nitric oxide mainly derived from endothelial cells; although ad renergic nerves appear to be responsible for the contraction, the tran smitter involved in the release of nitric oxide does not appear to be norepinephrine. The effects of L-NMMA in this preparation appear to be due to inhibition of nitric oxide formation rather than caused by cyc looxygenase activation.