Biphasic modulation of vascular nitric oxide catabolism by oxygen.
Endothelium-derived nitric oxide (NO) plays an important role in the regulation of vascular tone. Lack of NO bioavailability can result in cardiovascular disease. NO bioavailability is determined by its rates of generation and catabolism; however, it is not known how the NO catabolism rate is regulated in the vascular wall under normoxic, hypoxic, and anaerobic conditions. To investigate NO catabolism under different oxygen concentrations, studies of NO and O2 consumption by the isolated rat aorta were performed using electrochemical sensors. Under normoxic conditions, the rate of NO consumption in solution was enhanced in the presence of the rat aorta. Under hypoxic conditions, NO consumption decreased in parallel with the O2 concentration. Like the inhibition of mitochondrial respiration by NO, the inhibitory effects of NO on aortic O2 consumption increased as O2 concentration decreased. Under anaerobic conditions, however, a paradoxical reacceleration of NO consumption occurred. This increased anaerobic NO consumption was inhibited by the cytochrome c oxidase inhibitor NaCN but not by the free iron chelator deferoxamine, the flavoprotein inhibitor diphenylene iodonium (10 microM), or superoxide dismutase (200 U/ml). The effect of O2 on the NO consumption could be reproduced by purified cytochrome c oxidase (CcO), implying that CcO is involved in aortic NO catabolism. This reduced NO catabolism at low O2 tensions supports the maintenance of effective NO levels in the vascular wall, reducing the resistance of blood vessels. The increased anaerobic NO catabolism may be important for removing excess NO accumulation in ischemic tissues.
Liu
Xiaoping
X
Davis Heart and Lung Research Institute, The Ohio State Univ., 473 W. 12th Ave., Columbus, OH 43210, USA. Liu-11@medctr.osu.edu
Cheng
Crystal
C
Zorko
Nicholas
N
Cronin
Scott
S
Chen
Yeong-Renn
YR
Zweier
Jay L
JL
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D010100:Oxygen