Nitric oxide inhibits pulmonary artery catalase and H2O2-associated relaxation.
Our previous studies on the mechanism of relaxation of calf pulmonary arteries to H2O2 detected a role for increased formation of guanosine-3',5'-cyclic monophosphate as a result of a catalase-elicited activation of soluble guanylate cyclase. We have also shown that lactate elicits relaxation through increasing H2O2 produced from NADH oxidase-derived superoxide anion (O2-.). Because nitric oxide (NO) is a potential inhibitor of catalase, we examined the effects of exposure of endothelium-denuded bovine calf pulmonary arteries to an elevated physiological level of NO on relaxation to H2O2 and lactate. Treatment of pulmonary arteries with approximately 50 nM of NO gas for 2 min caused a subsequent inhibition of relaxation to H2O2 (10(-6) to 10(-3)M) and lactate (1-10 mM), without markedly altering relaxation responses to S-nitroso-N-acetylpenicillamine (10(-9) to 10(-6) M) or isoproterenol (10(-9) to 10(-6) M). This NO exposure caused a 63 and 70% inhibition of the metabolism by smooth muscle catalase of both endogenously produced and exogenous (100 microM) H2O2, respectively, as measured by the H2O2-dependent cooxidation of methanol to formaldehyde. A similar treatment of purified catalase with NO caused subsequent inhibition of its ability to metabolize H2O2, associated with changes in the spectra of catalase (increases in the absorbance at 535 and 570 nm) to a species that resembled compound II, an inactive form of catalase. The exposure of pulmonary arteries to NO also resulted in the detection of H2O2 release (by catalase-inhibitable luminol/ peroxidase-chemiluminescence). Thus exposure of pulmonary arteries to increased physiological levels of NO may promote altered vasoactive responses involving H2O2 as a result of the inhibition of catalase.
Mohazzab-H
K M
KM
Department of Physiology, New York Medical College, Valhalla 10595, USA.
Fayngersh
R P
RP
Wolin
M S
MS
D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors*; D002417:Cattle; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology*; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D019344:Lactic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D007545:Isoproterenol