Mechanism of carbon monoxide-induced relaxation in the guinea pig ileal smooth muscle

The mechanism of carbon monoxide (CO)-induced relaxation were investigated in the guinea-pig ileum. CO (10%) inhibited the 10 mM KCl-induced contracti on. This effect was antagonized by ODQ (1 muM), a soluble guanylate cyclase inhibitor. In contrast, CO did not inhibit the 40 mM KCl-induced increase in cytosolic Ca2+ level ([Ca2+](i)). Cumulative addition of KCI induced a g raded increase in both [Ca2+](i) and muscle tension. In the presence of CO, the increase in muscle tension was attenuated whereas the increase in [Ca2 +](i) was only slightly decreased. Thus, the [Ca2+](i)-tension relationship constructed by cumulative addition of KCl shifted downwards in the presenc e of CO. Using the patch clamp, CO was found to have little effect on the p eak Ba currents (I-Ba) when voltage was stepped from -60 mV to 0 mV. From t hese results, we conclude that CO inhibits contraction of guinea-pig ileum mainly by the decrease in the sensitivity of contractile elements to Ca2+ v ia a cyclic GMP-dependent pathway but not by the inhibition of L-type Ca2channel.