Effects of hypoxia and endothelium on myofilament Ca2+ sensitivity in α‐toxin‐permeabilized rat intrapulmonary arteries (IPA)

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is thought to require increases in both intracellular Ca2+ concentration ([Ca2+]) and myofilament Ca2+ sensitivity in pulmonary arterial smooth muscle. Furthermore, the increase in myofilament Ca2+ sensitivity caused by hypoxia may be due to factors derived from endothelium. To examine the effects of hypoxia and endothelium on Ca2+ sensitivity in pulmonary arterial smooth muscle, we measured the relationship between isometric tension and [Ca2+] at 37 °C in endothelium-intact (E+) and -denuded (E−) ∝-toxin-permeabilized rat IPA under normoxic (21%O2–5% CO2) and hypoxic (1% O2–5% CO2) conditions. Hypoxia increased the maximum contraction elicited by Ca2+ and decreased the [Ca2+] at which half-maximum contraction occurred in E+ and E- IPA. Endothelial denudation increased the maximum contraction elicited by Ca2+ and decreased the [Ca2+] required for half-maximum contraction in normoxic and hypoxic IPA. In both E+ and E- IPA, the effects of hypoxia were reduced or eliminated by pretreatment with the nitric oxide synthase inhibitor, Nω-Nitro-L-arginine methyl ester (L-NAME, 30 μM). These results suggest that hypoxia increased myofilament Ca2+sensitivity in permeabilized rat IPA, and that this effect was due in part to decreased production of NO in endothelium and smooth muscle. Funded by: HL75113 and HL67191