HYPERCAPNIC VASODILATATION IN ISOLATED RAT BASILAR ARTERIES IS EXERTED VIA LOW PH AND DOES NOT INVOLVE NITRIC-OXIDE SYNTHASE STIMULATION ORCYCLIC-GMP PRODUCTION

The relaxant effect of hypercapnia (15% CO2) was studied in isolated c ircular segments of rat basilar arteries with intact endothelium. The nitric oxide synthase inhibitor nitro-L-arginine (L-NOARG) and the cyt osolic guanylate cyclase inhibitor methylene blue (MB), significantly reduced this relaxation by 54% and 70%, respectively. The effect of L- NOARG was completely reversed by L-arginine. Blockade of nerve excitat ion with tetrodotoxin (TTX) had no affect on the 15% CO2 elicited vaso dilatation. Measurements of cGMP in vessel segments showed no signific ant increase in cGMP content in response to hypercapnia. L-NOARG and M B, but not TTX, significantly reduced the basal cGMP content in cerebr al vessels. Adding 1.5% halothane to the incubation medium did not res ult in a significant increase in cGMP content. Lowering the pH by cumu lative application of 0.12 M HCl resulted in relaxation identical to t hat obtained by lowering the pH with 15% CO2. In vessel segments in wh ich the endothelium had been removed beforehand 15% CO2 induced relaxa tion that was not different from that seen in vessels with intact endo thelium. L-NOARG had no affect in endothelium denuded vessels. The res ults suggest that high CO2 elicits vasodilatation of isolated rat basi lar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels by L-NOARG and MB suggest that there exists a basal NO formation in th e cerebral vessel wall.