title: Role of KATP and L-type Ca2+ channel activities in regulation of ovine uterine vascular contractility: effect of pregnancy and chronic hypoxia.
abstract: 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.
authors.affiliation: Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Daliao
authors.initials: D
authors.lastname: Xiao
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: 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
chemical_list: D020746:Calcium Channels, L-Type; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D014700:Verapamil
references.citation: Cardiovasc Res. 1994 Jun;28(6):797-804
references.pmid: 7923282
references.citation: Am J Physiol Heart Circ Physiol. 2000 Feb;278(2):H567-76
references.pmid: 10666089
references.citation: J Clin Invest. 1991 Aug;88(2):500-4
references.pmid: 1907614
references.citation: Am J Physiol. 1991 Mar;260(3 Pt 1):E464-70
references.pmid: 2003600
references.citation: Circ Res. 1991 Nov;69(5):1415-20
references.pmid: 1934364
references.citation: J Appl Physiol (1985). 2002 Apr;92(4):1692-701
references.pmid: 11896039
references.citation: J Cardiovasc Pharmacol. 2005 Feb;45(2):99-108
references.pmid: 15654257
references.citation: J Neurophysiol. 2000 Sep;84(3):1636-44
references.pmid: 10980033
references.citation: Microcirculation. 2005 Jan-Feb;12(1):113-27
references.pmid: 15804979
references.citation: Am J Physiol. 1992 May;262(5 Pt 1):C1220-7
references.pmid: 1590361
references.citation: Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H71-80
references.pmid: 16489108
references.citation: Am J Physiol. 1995 Apr;268(4 Pt 1):C799-822
references.pmid: 7733230
references.citation: Biol Reprod. 2004 Apr;70(4):1171-7
references.pmid: 14681203
references.citation: Hypertension. 2008 Jul;52(1):156-62
references.pmid: 18474836
references.citation: Science. 1989 Jul 14;245(4914):177-80
references.pmid: 2501869
references.citation: J Cardiovasc Pharmacol. 2004 Nov;44(5):525-31
references.pmid: 15505488
references.citation: Am J Obstet Gynecol. 1982 Oct 15;144(4):423-9
references.pmid: 7124861
references.citation: J Biol Chem. 2008 Feb 1;283(5):2488-94
references.pmid: 18048350
references.citation: Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H142-8
references.pmid: 15358611
references.citation: Pediatr Res. 2001 Apr;49(4):490-4
references.pmid: 11264431
references.citation: Am J Obstet Gynecol. 1993 Dec;169(6):1510-6
references.pmid: 8267055
references.citation: Am J Physiol Regul Integr Comp Physiol. 2000 Feb;278(2):R295-303
references.pmid: 10666128
references.citation: Am J Physiol Heart Circ Physiol. 2002 Jan;282(1):H292-300
references.pmid: 11748074
references.citation: Annu Rev Physiol. 2001;63:259-87
references.pmid: 11181957
references.citation: Am J Physiol Heart Circ Physiol. 2001 Jul;281(1):H422-31
references.pmid: 11406511
references.citation: Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H812-20
references.pmid: 11158981
references.citation: Circ Res. 1994 May;74(5):1005-8
references.pmid: 8156623
references.citation: Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1840-9
references.pmid: 19376810
references.citation: Am J Physiol. 1992 Aug;263(2 Pt 2):H399-404
references.pmid: 1510137
references.citation: FASEB J. 2005 Jan;19(1):150-2
references.pmid: 15494446
references.citation: J Smooth Muscle Res. 2008 Apr;44(2):65-81
references.pmid: 18552454
references.citation: Am J Physiol. 1998 Aug;275(2):H680-8
references.pmid: 9683458
references.citation: Stroke. 1996 Oct;27(10):1874-80; discussion 1880-1
references.pmid: 8841347
references.citation: Am J Physiol. 1990 Jul;259(1 Pt 1):C3-18
references.pmid: 2164782
references.citation: Am J Physiol. 1993 Jan;264(1 Pt 2):H8-13
references.pmid: 8430866
references.citation: J Physiol. 1993 Dec;472:1-9
references.pmid: 8145135