Cellular mechanisms of nitric oxide-induced relaxation of corporeal smooth muscle in the guinea-pig

The cellular mechanism of nitric oxide (NO)-induced relaxation in corporeal smooth muscle (CSM) of the guinea-pig was investigated. Changes in the intracellular concentration of calcium ions ([Ca 2+ ] i ), membrane potential and isometric tension were measured. CSM cells exhibited spontaneous depolarizations and transient increases in [Ca 2+ ] i (Ca 2+ transients) which were accompanied by contractions. This spontaneous activity was abolished by nifedipine (10 μ m ). NO released by 3-morpholino-sydnonimine (SIN-1, 10 μ m ) hyperpolarized the membrane and prevented the generation of spontaneous depolarizations. SIN-1 also abolished Ca 2+ transients and associated contractions. These effects of SIN-1 were blocked by 1 H -[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 μ m ), an inhibitor of guanylate cyclase. Noradrenaline (NA, 1 μ m ) increased [Ca 2+ ] i to levels similar to those produced by high potassium-containing solution (high K + solution, [K + ] o = 40 m m ), however, NA-induced contractions were three times greater in amplitude than those induced by high K + solution. In NA precontracted preparations, SIN-1 inhibited 80 % of the contraction and decreased [Ca 2+ ] i by 20 %. In contrast, nifedipine reduced [Ca 2+ ] i by 80 %, while the level of contraction was decreased by only 20 %. SIN-1-induced reduction in [Ca 2+ ] i but not the tension effect, was abolished by pretreatment with cyclopiazonic acid (CPA, 10 μ m ). In high K + precontracted preparations, SIN-1 inhibited 80 % of the contraction and reduced [Ca 2+ ] i by 20 %. Nifedipine, however, largely abolished increases in both [Ca 2+ ] i and tension under these circumstances. These results suggest that decreasing the sensitivity of contractile proteins to Ca 2+ is probably the key mechanism of NO-induced relaxation in CSM of the guinea-pig.