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Effects of hypoxia and endothelium on myofilament Ca2+ sensitivity in α‐toxin‐permeabilized rat intrapulmonary arteries (IPA)
Author(s) -
Weigand Letitia,
Shimoda Larissa A,
Sylvester J T
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1437-b
Subject(s) - myofilament , contraction (grammar) , hypoxia (environmental) , vasoconstriction , hypoxic pulmonary vasoconstriction , endothelium , nitric oxide , medicine , endocrinology , chemistry , anatomy , biology , myocyte , oxygen , organic chemistry
Hypoxic pulmonary vasoconstriction (HPV) is thought to require increases in both intracellular Ca 2+ concentration ([Ca 2+ ]) and myofilament Ca 2+ sensitivity in pulmonary arterial smooth muscle. Furthermore, the increase in myofilament Ca 2+ sensitivity caused by hypoxia may be due to factors derived from endothelium. To examine the effects of hypoxia and endothelium on Ca 2+ sensitivity in pulmonary arterial smooth muscle, we measured the relationship between isometric tension and [Ca 2+ ] at 37 °C in endothelium‐intact (E+) and ‐denuded (E−) ∝‐toxin‐permeabilized rat IPA under normoxic (21%O 2 –5% CO 2 ) and hypoxic (1% O 2 –5% CO 2 ) conditions. Hypoxia increased the maximum contraction elicited by Ca 2+ and decreased the [Ca 2+ ] at which half‐maximum contraction occurred in E+ and E‐ IPA. Endothelial denudation increased the maximum contraction elicited by Ca 2+ and decreased the [Ca 2+ ] 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 Ca 2+ 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