CARBON MONOXIDE-INDUCED VASORELAXATION AND THE UNDERLYING MECHANISMS

1 Carbon monoxide (CO) induced a concentration-dependent relaxation of isolated rat tail artery tissues which were precontracted with phenyl ephrine or U-46619. This vasorelaxing effect of CO was independent of the presence of the intact endothelium. 2 The CO-induced vasorelaxatio n was partially inhibited by the blockade of either the cyclicGMP path way or big-conductance calcium-activated K (K-Ca) channels. When both the cyclicGMP pathway and K-Ca channels were blocked, the CO-induced v asorelaxation was completely abolished. 3 Incubation of vascular tissu es with hemin, in order to enhance the endogenous production of CO, su ppressed the phenylephrine-induced vasocontraction in a time- and conc entration-dependent manner. The hemin-induced suppression of the vascu lar contractile response to phenylephrine was abolished after the vasc ular tissues were co-incubated with either oxyhaemoglobin or zinc prot oporphyrin-IX, suggesting an induced endogenous generation of CO from vascular tissues. 4 The effect of hemin incubation on vascular contrac tility did not involve the endogenous generation of nitric oxide. 5 Ou r results suggest that CO may activate both a cyclicGMP signalling pat hway and K-Ca channels in the same vascular tissues, and that the endo genously generated CO may significantly affect the vascular contractil e responses.