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 activati on of soluble guanylate cyclase. We have also shown that lactate elici ts relaxation through increasing H2O2 produced from NADH oxidase-deriv ed superoxide anion (O-2(-).). Because nitric oxide (NO) is a potentia l inhibitor of catalase, we examined the effects of exposure of endoth elium-denuded bovine calf pulmonary arteries to an elevated physiologi cal level of NO on relaxation to H2O2 and lactate. Treatment of pulmon ary arteries with similar to 50 nM of NO gas for 2 min caused a subseq uent inhibition of relaxation to H2O2 (10(-6) to 10(-3) M) and lactate (1-10 mM), without markedly altering relaxation responses to S-nitros o-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 m etabolism by smooth mascle catalase of both endogenously produced and exogenous (100 mu M) H2O2, respectively, as measured by the H2O2-depen dent cooxidation of methanol to formaldehyde. A similar treatment of p urified catalase with NO caused subsequent inhibition of its ability t o metabolize H2O2, associated with changes in the spectra of catalase (increases in the absorbance at 535 and 570 nm) to a species that rese mbled compound 4 an inactive form of catalase. The exposure of pulmona ry arteries to NO also resulted in the detection of H2O2 release (by c atalase-inhibitable luminol/peroxidase-chemiluminescence). Thus exposu re of pulmonary arteries to increased physiological levels of NO may p romote altered vasoactive responses involving H2O2 as a result of the inhibition of catalase.