TY - JOUR
T1 - Voltage-independent calcium entry in hypoxic pulmonary vasoconstriction of intrapulmonary arteries of the rat
AU - Robertson, T P
AU - Hague, D
AU - Aaronson, P I
AU - Ward, J P T
PY - 2000/6/15
Y1 - 2000/6/15
N2 - 1. It has been proposed that hypoxic pulmonary vasoconstriction (HPV) is mediated via K+ channel inhibition and Ca2+ influx through voltage-gated channels. HPV depends strongly on the degree of preconstriction, and Lte therefore examined thtr effect of Ca2+ channel blockade on tension and intracellular [Ca2+] ([Ca2+](i)) during HPV in rat intrapulmonary arteries (IPAs), whilst maintaining preconstriction constant. We also investigated the role of intracellular Ca2+ stores. 2. HPV demonstrated a transient constriction (phase I) superimposed on a sustained constriction (phase II). Nifedipine (1 mu M) partially inhibited phase I, but did not affect phase II. In arteries exposed to 80 mM K+ and nifedipine or diltiazem the rises in tension and [Ca2+](i) were blunted during phase I, but were unaffected during phase II. 3. At low concentrations (<3 mu M), La3+ almost abolished the phase I constriction and rise in [Ca2+](i), but had no effect on phase II, or constriction in response to 80 mM K+. Phase II was inhibited by higher concentrations of La3+ (IC50 similar to 50 mu M). 4. IPA treated with thapsigargin (1 mu M) in Ca2+-free solution to deplete Ca2+ stores showed sustained constriction upon re-exposure to Ca2+ and an increase in the rate of Mn2+ influx, suggesting capacitative Ca2+ entry The concentration dependency of the block of constriction by La3+ was similar to that for phase I of HPV. Pretreatment of TPA with 30 mu M CPA reduced phase I by > 80%, but had no significant effect on phase II. 5. We conclude that depolarization-mediated Ca2+ 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 Ca2+ entry related to release of thapsigargin-sensitive Ca2+ stores, whereas phase II is supported by Ca2+ entry via a separate voltage-independent pathway.
AB - 1. It has been proposed that hypoxic pulmonary vasoconstriction (HPV) is mediated via K+ channel inhibition and Ca2+ influx through voltage-gated channels. HPV depends strongly on the degree of preconstriction, and Lte therefore examined thtr effect of Ca2+ channel blockade on tension and intracellular [Ca2+] ([Ca2+](i)) during HPV in rat intrapulmonary arteries (IPAs), whilst maintaining preconstriction constant. We also investigated the role of intracellular Ca2+ stores. 2. HPV demonstrated a transient constriction (phase I) superimposed on a sustained constriction (phase II). Nifedipine (1 mu M) partially inhibited phase I, but did not affect phase II. In arteries exposed to 80 mM K+ and nifedipine or diltiazem the rises in tension and [Ca2+](i) were blunted during phase I, but were unaffected during phase II. 3. At low concentrations (<3 mu M), La3+ almost abolished the phase I constriction and rise in [Ca2+](i), but had no effect on phase II, or constriction in response to 80 mM K+. Phase II was inhibited by higher concentrations of La3+ (IC50 similar to 50 mu M). 4. IPA treated with thapsigargin (1 mu M) in Ca2+-free solution to deplete Ca2+ stores showed sustained constriction upon re-exposure to Ca2+ and an increase in the rate of Mn2+ influx, suggesting capacitative Ca2+ entry The concentration dependency of the block of constriction by La3+ was similar to that for phase I of HPV. Pretreatment of TPA with 30 mu M CPA reduced phase I by > 80%, but had no significant effect on phase II. 5. We conclude that depolarization-mediated Ca2+ 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 Ca2+ entry related to release of thapsigargin-sensitive Ca2+ stores, whereas phase II is supported by Ca2+ entry via a separate voltage-independent pathway.
UR - http://www.scopus.com/inward/record.url?scp=0034659397&partnerID=8YFLogxK
U2 - 10.1111/j.1469-7793.2000.t01-1-00669.x
DO - 10.1111/j.1469-7793.2000.t01-1-00669.x
M3 - Article
SN - 1469-7793
VL - 525
SP - 669
EP - 680
JO - The Journal of Physiology
JF - The Journal of Physiology
IS - 3
ER -