Enhancement of myofilament calcium sensitivity by acute hypoxia in rat distal pulmonary arteries

Letitia Weigand, Larissa A. Shimoda, J. T. Sylvester

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxic contraction of pulmonary arterial smooth muscle is thought to require increases in both intracellular Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity, which may or may not be endothelium-dependent. To examine the effects of hypoxia and endothelium on Ca2+ sensitivity in pulmonary arterial smooth muscle, we measured the relation between [Ca2+]i and isometric force at 37°C during normoxia (21% O2-5% CO2) and after 30 min of hypoxia (1% O2-5% CO2) in endothelium-intact (E+) and -denuded (E-) rat distal intrapulmonary arteries (IPA) permeabilized with staphylococcal α-toxin. Endothelial denudation enhanced Ca2+ sensitivity during normoxia but did not alter the effects of hypoxia, which shifted the [Ca2+]i-force relation to higher force in E+ and E- IPA. Neither hypoxia nor endothelial denudation altered Ca2+ sensitivity in mesenteric arteries. In E+ and E- IPA, hypoxic enhancement of Ca2+ sensitivity was abolished by the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester (30 μM), which shifted normoxic [Ca2+]i-force relations to higher force. In E- IPA, the Rho kinase antagonist Y-27632 (10 μM) shifted the normoxic [Ca2+]i-force relation to lower force but did not alter the effects of hypoxia. These results suggest that acute hypoxia enhanced myofilament Ca2+ sensitivity in rat IPA by decreasing nitric oxide production and/or activity in smooth muscle, thereby revealing a high basal level of Ca2+ sensitivity, due in part to Rho kinase, which otherwise did not contribute to Ca2+ sensitization by hypoxia.

Original languageEnglish (US)
Pages (from-to)L380-L387
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number3
DOIs
StatePublished - Sep 2011

Keywords

  • Endothelin-1
  • Endothelium
  • N-nitro-L-arginine methyl ester
  • Nitric oxide
  • Rho kinase
  • Temperature
  • Vascular smooth muscle
  • Y-27632

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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