Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation.
Hydrogen peroxide produces concentration-dependent relaxation of precontracted isolated bovine intrapulmonary arterial rings by a mechanism which is independent of the endothelium or prostaglandin mediators. Relaxant responses to hydrogen peroxide concentrations of up to 100 microM were markedly attenuated by the inhibitor of soluble guanylate cyclase activation, methylene blue (10 microM). Micromolar concentrations of hydrogen peroxide elicit time- and concentration-dependent increase in arterial levels of guanosine 3',5'-cyclic monophosphate that are associated with decreases in force. Soluble guanylate cyclase activity is markedly activated by enzymatically generated hydrogen peroxide in a manner that is most closely associated with the concentration of catalase present in the assay, by a mechanism that is inhibited by superoxide anion and the inactivation of catalase. Our data are most consistent with the involvement of compound I, a species of catalase formed during the metabolism of peroxide, in the mechanism of guanylate cyclase activation. The nature of this mechanism of arterial relaxation suggests that it could contribute to the regulation of pulmonary vascular tone by oxygen tension.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000502:physiology; D002417:Cattle; D006152:Cyclic GMP / Q000502:physiology; D004727:Endothelium / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005949:Glucose Oxidase / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects
D012701:Serotonin; D006632:Histamine; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D002374:Catalase; D013482:Superoxide Dismutase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; D008751:Methylene Blue; D007213:Indomethacin