title: Hypercapnia relaxes cerebral arteries and potentiates neurally-induced relaxation.
abstract: The present study was designed to determine whether relaxations induced by hypercapnia depend upon nitric oxide (NO) derived from the endothelium, and whether NO-mediated relaxant response to electrical and chemical stimulation of vasodilator nerves is modulated by hypercapnia. In canine and monkey cerebral arterial strips contracted with K+, raising the level of CO2 of the aerating gas in the bathing media from 5 to 10% produced a moderate relaxation, together with an increased Pco2 (from 29.8 to 59.3 mm Hg) and a decreased pH (from 7.43 to 7.15). Relaxation was not influenced by endothelium denudation and treatment with NG-nitro-L-arginine. Contractions elicited by the NO synthase inhibitor were attenuated by the removal of the endothelium. Relaxations, caused by transmural electrical stimulation and nicotine, of canine cerebral arterial strips contracted with prostaglandin F2 alpha, were potentiated only slightly by hypercapnia, but the potentiation of the response to exogenous NO (acidified NaNO2) was clearly greater. It is concluded that as far as the arteries used are concerned, hypercapnia does not seem to liberate NO from the endothelium but does potentiate the effect of NO. The reason for lesser potentiation, by hypercapnia, of the response to nitroxidergic nerve stimulation than to NO action may be associated with an impairment by intracellular acidosis of NO synthase activation.
authors.affiliation: Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Toda
authors.forename: K
authors.initials: K
authors.lastname: Ayajiki
authors.forename: T
authors.initials: T
authors.lastname: Okamura
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008251:Macaca; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; D009538:Nicotine; D001120:Arginine; D019001:Nitric Oxide Synthase; D011188:Potassium