Hypoxia-induced inhibition of the response to nitroxidergic nerve stimulation in canine cerebral arteries.
In isolated canine middle cerebral arteries contracted with prostaglandin F2 alpha, transmural electrical stimulation (TES), nicotine, and substance P produced relaxations. Transmural electrical stimulation- and nicotine-induced endothelium-independent responses are mediated by nitric oxide (NO) liberated from perivascular nerve, whereas substance P-induced relaxations are mediated by endothelium-derived NO. These responses were attenuated by replacement of 95% O2 and 5% CO2 gas (about 550 mm Hg of partial O2 pressure) with 95% N2 and 5% CO2 gas (about 40 mm Hg); inhibition of the response to TES was stabilized 30 minutes later. Reoxygenation partially reversed the response. Relaxations caused by exogenous NO were not influenced by hypoxia. Inhibition by hypoxia of the response to TES was not affected by superoxide dismutase. However, the inhibitory effect was prevented by amiloride and dimethyl-amiloride, Na(+)-H+ exchange inhibitors, or acidosis caused by the addition of HCl. The inhibition by hypoxia was reversed by amiloride. It is concluded that depression by hypoxia of the response mediated by endogenous NO is associated with impaired membrane function caused by restoration of normal intracellular pH by Na(+)-H+ exchanger.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Ayajiki
K
K
Toda
N
N
D000138:Acidosis / Q000503:physiopathology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation*; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009424:Nervous System Physiological Phenomena; D009433:Neural Inhibition; D009569:Nitric Oxide / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D009569:Nitric Oxide; D013373:Substance P; C039465:5-dimethylamiloride; D000584:Amiloride; D013482:Superoxide Dismutase