Endothelium-independent contractions to NG-monomethyl-L-arginine in canine basilar artery.

Abstract

NG-substituted analogues of L-arginine are potent and selective inhibitors of nitric oxide synthase(s). The present study was designed to determine the effects of these analogues on the vascular smooth muscle of isolated canine basilar arteries. Basilar artery rings without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (temperature = 37 degrees C, pH = 7.4). A radioimmunoassay technique was used to determine the levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP). NG-Monomethyl-L-arginine (L-NMMA) caused concentration-dependent contractions, whereas the D-enantiomer and NG-nitro-L-arginine did not. Contractions to L-NMMA were reduced in the presence of L-arginine but not in the presence of D-arginine. Superoxide anions generated by xanthine plus xanthine oxidase in the presence of catalase abolished contractions to L-NMMA but did not affect contractions to the prostaglandin H2/thromboxane A2 agonist U46619. Zaprinast, a selective cyclic GMP phosphodiesterase inhibitor, caused concentration-dependent relaxations. L-NMMA selectively inhibited these relaxations. The inhibitory effect of L-NMMA was reversed in the presence of L-arginine. L-NMMA selectively reduced the basal production of cyclic GMP. These studies suggest that in cerebral arteries, contractions of smooth muscle cells to L-NMMA are mediated by inhibition of nitric oxide synthase with a resultant decrease in the basal production of nitric oxide.