INHIBITION BY ZINC PROTOPORPHYRIN-IX OF VASOACTIVE INTESTINAL PEPTIDE-INDUCED RELAXATIONS OF GUINEA-PIG ISOLATED TRACHEA

Carbon monoxide, formed as a product of heme oxygenase activity, has b een postulated to act as an intra- and intercellular messenger molecul e. We addressed the hypothesis that heme oxygenase is involved in the relaxation of the guinea pig trachealis elicited by vasoactive intesti nal peptide (VIP) or by electrical field stimulation. Immunohistochemi cal studies revealed the presence of heme oxygenase-II in airway smoot h muscle and epithelium. Zinc protoporphyrin-IX (ZnPPn), an inhibitor of heme oxygenase, effectively inhibited VIP-induced relaxations of tr acheal smooth muscle. Surprisingly, the potency of ZnPPn was increased if the drug was preincubated with the VIP solution before addition to the tissue bath. The relaxant responses to 3-morpholinosydnonimine we re unaffected by ZnPPn. Zinc deuteroporphyrin-IX 2,4 bisglycol, a more potent inhibitor of heme oxygenase than ZnPPn, did not affect the VIP responses. ZnPPn (300 mu M) had no effect on nonadrenergic, noncholin ergic relaxations of the guinea pig trachea. These data indicate that although ZnPPn is an efficacous inhibitor of VIP-induced relaxations o f the guinea pig trachealis, it is unlikely that heme oxygenase plays an important role in this response. Rather, the data are consistent wi th the hypothesis that ZnPPn inhibits the VIP response via an interact ion with the VIP molecules themselves. Although the results demonstrat e the existence of heme oxygenase-II in the guinea pig trachealis, the y do not support the hypothesis that it plays a role in electrical fie ld stimulation-induced nonadrenergic, noncholinergic relaxations.