title: 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.
authors.affiliation: Department of Experimental Research, Malmö General Hospital, Sweden.
authors.forename: J P
authors.initials: JP
authors.lastname: You
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: I
authors.initials: I
authors.lastname: Jansen-Olesen
authors.forename: O B
authors.initials: OB
authors.lastname: Paulson
authors.forename: N A
authors.initials: NA
authors.lastname: Lassen
authors.forename: L
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000502:physiology*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D019335:Nitroarginine; D013779:Tetrodotoxin; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D008751:Methylene Blue