Role of KATP and L-type Ca2+ channel activities in regulation of ovine uterine vascular contractility: effect of pregnancy and chronic hypoxia.
OBJECTIVE
Our objective was to determine whether the pregnancy and high altitude long-term hypoxia-mediated changes in uterine artery contractility were regulated by K(ATP) and L-type Ca(2+) channel activities.


METHODS
Uterine arteries were isolated from nonpregnant and near-term pregnant ewes that had been maintained at sea level (∼300 m) or exposed to high altitude (3801 m) for 110 days. Isometric tension was measured in a tissue bath.


RESULTS
Pregnancy increased diazoxide, but not verapamil-induced relaxations. Long-term hypoxia attenuated diazoxide-induced relaxations in near-term pregnant uterine arteries, but enhanced verapamil-induced relaxations in nonpregnant uterine arteries. Diazoxide decreased the maximal response (E(max)) of phenylephrine-induced contractions in near-term pregnant uterin arteries but not nonpregnant uterine arteries in normoxic sheep. In contrast, diazoxide had no effect on phenylephrine-induced E(max) in near-term pregnant uterine arteries but decreased it in nonpregnant uterine arteries in long-term hypoxia animals. Verapamil decreased the E(max) and pD(2) (-logEC(50)) of phenylephrine-induced contractions in both nonpregnant uterine arteries and near-term pregnant uterine arteries in normoxic and long-term hypoxia animals, except nonpregnant uterine arteries of normoxic animals in which verapamil showed no effect on the pD(2).


CONCLUSIONS
The results suggest that pregnancy selectively increases K(ATP), but not L-type Ca(2+) channel activity. Long-term hypoxia decreases the K(ATP) channel activity, which may contribute to the enhanced uterine vascular myogenic tone observed in pregnant sheep at high altitude hypoxia.
Xiao
Daliao
D
Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Longo
Lawrence D
LD
Zhang
Lubo
L
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000531:Altitude; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011897:Random Allocation; D012016:Reference Values; D012756:Sheep; D034561:Sheep, Domestic; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D014700:Verapamil
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