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 phenylephrine or U-46619. This vasorelaxing effect of CO was independent of the presence of the intact endothelium. 2 The CO-induced vasorelaxation was partially inhibited by the blockade of either the cyclicGMP pathway or big-conductance calcium-activated K (K-Ca) channels. When both the cyclicGMP pathway and K-Ca channels were blocked, the CO-induced vasorelaxation was completely abolished. 3 Incubation of vascular tissues with hemin, in order to enhance the endogenous production of CO, suppressed the phenylephrine-induced vasocontraction in a time- and concentration-dependent manner. The hemin-induced suppression of the vascular contractile response to phenylephrine was abolished after the vascular tissues were co-incubated with either oxyhaemoglobin or zinc protoporphyrin-IX, suggesting an induced endogenous generation of CO from vascular tissues. 4 The effect of hemin incubation on vascular contractility did not involve the endogenous generation of nitric oxide. 5 Our results suggest that CO may activate both a cyclicGMP signalling pathway and K-Ca channels in the same vascular tissues, and that the endogenously generated CO may significantly affect the vascular contractile responses.