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Voltage‐independent calcium entry in hypoxic pulmonary vasoconstriction of intrapulmonary arteries of the rat
Author(s) -
Robertson T. P.,
Hague D.,
Aaronson P. I.,
Ward J. P. T.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.t01-1-00669.x
Subject(s) - nifedipine , constriction , vasoconstriction , hypoxic pulmonary vasoconstriction , chemistry , depolarization , medicine , biophysics , endocrinology , calcium , diltiazem , biology
1 It has been proposed that hypoxic pulmonary vasoconstriction (HPV) is mediated via K + channel inhibition and Ca 2+ influx through voltage‐gated channels. HPV depends strongly on the degree of preconstriction, and we therefore examined the effect of Ca 2+ channel blockade on tension and intracellular [Ca 2+ ] ([Ca 2+ ] i ) during HPV in rat intrapulmonary arteries (IPAs), whilst maintaining preconstriction constant. We also investigated the role of intracellular Ca 2+ stores. 2 HPV demonstrated a transient constriction (phase I) superimposed on a sustained constriction (phase II). Nifedipine (1 μ m ) partially inhibited phase I, but did not affect phase II. In arteries exposed to 80 m m K + and nifedipine or diltiazem the rises in tension and [Ca 2+ ] i were blunted during phase I, but were unaffected during phase II. 3 At low concentrations (< 3 μ m ), La 3+ almost abolished the phase I constriction and rise in [Ca 2+ ] i , but had no effect on phase II, or constriction in response to 80 m m K + . Phase II was inhibited by higher concentrations of La 3+ (IC 50 ∼50 μ m ). 4 IPA treated with thapsigargin (1 μ m ) in Ca 2+ ‐free solution to deplete Ca 2+ stores showed sustained constriction upon re‐exposure to Ca 2+ and an increase in the rate of Mn 2+ influx, suggesting capacitative Ca 2+ entry. The concentration dependency of the block of constriction by La 3+ was similar to that for phase I of HPV. Pretreatment of IPA with 30 μ m CPA reduced phase I by > 80%, but had no significant effect on phase II. 5 We conclude that depolarization‐mediated Ca 2+ influx plays at best a minor role in the transient phase I constriction of HPV, and is not involved in the sustained phase II constriction. Instead, phase I appears to be mainly dependent on capacitative Ca 2+ entry related to release of thapsigargin‐sensitive Ca 2+ stores, whereas phase II is supported by Ca 2+ entry via a separate voltage‐independent pathway.