Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production

Abstract

The relaxant effect of hypercapnia (15% CO₂) was studied in isolated circular segments of rat basilar arteries with intact endothelium. The nitric oxide synthase inhibitor nitro‐l‐arginine (l‐NOARG) and the cytosolic 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 excitation with tetrodotoxin (TTX) had no affect on the 15% CO₂ elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response to hypercapnia. l‐NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 m HCl resulted in relaxation identical to that obtained by lowering the pH with 15% CO₂. In vessel segments in which the endothelium had been removed beforehand 15% CO₂ induced relaxation that was not different from that seen in vessels with intact endothelium. l‐NOARG had no affect in endothelium denuded vessels. The results suggest that high CO₂ elicits vasodilatation of isolated rat basilar 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 the cerebral vessel wall.