title: Cellular mechanisms of nitric oxide-induced relaxation of corporeal smooth muscle in the guinea-pig.
abstract: 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 microM). NO released by 3-morpholino-sydnonimine (SIN-1, 10 microM) 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 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 microM), an inhibitor of guanylate cyclase. Noradrenaline (NA, 1 microM) increased [Ca(2+)](i) to levels similar to those produced by high potassium-containing solution (high K(+) solution, [K(+)](o) = 40 mM), 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 microM). 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.
authors.affiliation: Department of Physiology, Nagoya City University Medical School, Nagoya 467-8601, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Fukuta
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Dickens
authors.forename: Hikaru
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D010413:Penis / Q000187:drug effects* / Q000502:physiology*; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D012996:Solutions / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020030:Nitric Oxide Donors; D012996:Solutions; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine