Role of Carbon Monoxide in the Mechanisms of Action of Extracellular ATP on Contractile Activity of Vascular Smooth Muscle Cells

We studied the role of carbon monoxide (CO) in the effect of P2X and P2Y receptor agonist ATP on the tone of rat aorta segments with intact endothelium. ATP (1-1000 μM) and P2X receptor agonist α,β-MeATP (100 μM) relaxed segments precontracted with phenylephrine (10 μM), while UTP (100-1000 μM) increased the amplitude of phenylephrine-induced contraction. The relaxing effect of ATP was enhanced by CORM II (100 μM), NO synthase inhibitor L-NAME, and guanylate cyclase inhibitor ODQ and attenuated by ZnPP IX (100 μM). The constrictive effect of UTP was weakened by CORM II (100 μM), but was not changed by ZnPP IX (100 μM). ZnPP IX (100 μM) weakened the relaxation response to α,β-MeATP. Thus, ATP involves the CO-dependent signaling cascade through P2X receptors.