INHIBITION BY ZINC PROTOPORPHYRIN-IX OF RECEPTOR-MEDIATED RELAXATION OF THE RAT AORTA IN A MANNER DISTINCT FROM INHIBITION OF HEME OXYGENASE

1 Carbon monoxide (CO), produced by aem oxygenase through degradation of haem, has been claimed to be a neuromessenger and a possible regula tor of vascular tone. We examined whether the haem oxygenase inhibitor , zinc protoporphyrin-IX (ZnPP) and other porphyrins affect the relaxa tion evoked by various agents in the rat isolated aorta. 2 Pretreatmen t with ZnPP (0.1 mM) virtually abolished the relaxation evoked by vaso active intestinal peptide (VIP) and atrial natriuretic peptide (ANP). ZnPP also evoked a rightward shift of the concentration-response curve for the relaxation induced by acetylcholine. 3 In contrast, ZnPP did not affect the relaxation evoked by forskolin and 3-morpholino-sydnoni mine, agents which directly activate adenylate and guanylate cyclase, respectively. 4 Although, less effective than ZnPP, tin protoporphyrin -IX (SnPP; 0.1 mM) and protoporphyrin-IX (PP; 0.1 mM) also attenuated the VIP-evoked relaxation. 5 The elevation of cyclic AMP and cyclic GM P levels evoked by VIP and ANP; respectively, were abolished by pretre atment with ZnPP (0.1 mM). 6 ZnPP, SnPP and PP did not affect the cont raction evoked by phenylephrine. 7 The results show that ZnPP inhibits relaxation induced by VIP, ANP and acetylcholine, probably by interfe ring with membrane receptor-coupled signal transduction pathways. This inhibition does not seem to be dependent upon inhibition of haem oxyg enase. The lack of specificity of the haem oxygenase inhibiting metall oporphyrins makes them less suitable as pharmacological tools in the i nvestigation of a messenger role for CO.