title: Enhancement of myofilament calcium sensitivity by acute hypoxia in rat distal pulmonary arteries.
abstract: Hypoxic contraction of pulmonary arterial smooth muscle is thought to require increases in both intracellular Ca(2+) concentration ([Ca(2+)](i)) and myofilament Ca(2+) sensitivity, which may or may not be endothelium-dependent. To examine the effects of hypoxia and endothelium on Ca(2+) sensitivity in pulmonary arterial smooth muscle, we measured the relation between [Ca(2+)](i) and isometric force at 37°C during normoxia (21% O(2)-5% CO(2)) and after 30 min of hypoxia (1% O(2)-5% CO(2)) in endothelium-intact (E+) and -denuded (E-) rat distal intrapulmonary arteries (IPA) permeabilized with staphylococcal α-toxin. Endothelial denudation enhanced Ca(2+) sensitivity during normoxia but did not alter the effects of hypoxia, which shifted the [Ca(2+)](i)-force relation to higher force in E+ and E- IPA. Neither hypoxia nor endothelial denudation altered Ca(2+) sensitivity in mesenteric arteries. In E+ and E- IPA, hypoxic enhancement of Ca(2+) sensitivity was abolished by the nitric oxide synthase inhibitor N(ω)-nitro-l-arginine methyl ester (30 μM), which shifted normoxic [Ca(2+)](i)-force relations to higher force. In E- IPA, the Rho kinase antagonist Y-27632 (10 μM) shifted the normoxic [Ca(2+)](i)-force relation to lower force but did not alter the effects of hypoxia. These results suggest that acute hypoxia enhanced myofilament Ca(2+) sensitivity in rat IPA by decreasing nitric oxide production and/or activity in smooth muscle, thereby revealing a high basal level of Ca(2+) sensitivity, due in part to Rho kinase, which otherwise did not contribute to Ca(2+) sensitization by hypoxia.
authors.affiliation: Div. of Pulmonary and Critical Care Medicine, The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Cir., Baltimore, MD 21224, USA.
authors.forename: Letitia
authors.initials: L
authors.lastname: Weigand
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Shimoda
authors.forename: J T
authors.initials: JT
authors.lastname: Sylvester
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D054460:rho-Associated Kinases; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester