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 (KCa) channels. When both the cyclicGMP pathway and KCa 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 KCa channels in the same vascular tissues, and that the endogenously generated CO may significantly affect the vascular contractile responses.
Wang
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Departement de physiologie, Université de Montreal, Québec, Canada.
Wang
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Wu
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D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology / Q000502:physiology; D006427:Hemin / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000098:blood supply
D015221:Potassium Channels; D006427:Hemin; D002248:Carbon Monoxide; D006152:Cyclic GMP; D002118:Calcium