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BOR - Papers in Press, published online ahead of print February 25, 2004.
Biol Reprod 2004, 10.1095/biolreprod.103.026708
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BIOLOGY OF REPRODUCTION 71, 156–162 (2004)
DOI: 10.1095/biolreprod.103.026708
© 2004 by the Society for the Study of Reproduction, Inc.

Female Reproductive Tract

Long-Term Hypoxia Alters Calcium Regulation in Near-Term Ovine Myometrium1

T.K. Arakawa, M. Mlynarczyk, K.M. Kaushal, L. Zhang, and C.A. Ducsay2

Center for Perinatal Biology, Departments of Physiology/Pharmacology and Pediatrics, Loma Linda University School of Medicine, Loma Linda, California 92350

Previous studies showed that long-term hypoxia (LTH) during pregnancy alters myometrial contractility. The present study was designed to test the hypothesis that LTH during pregnancy suppresses myometrial contractility in sheep by affecting the calcium signaling cascade. Pregnant sheep were maintained at high altitude (3820 m) from Day 30 to Day 139 of gestation, when the animals were killed for collection of myometrial tissue. Tissue was also collected from age-matched, normoxic controls. Circular and longitudinal layers were separated, and strips from each layer were mounted in a muscle bath. After pretreatment with 10–8 M oxytocin, the strips were exposed to increasing half- or quarter-log doses of nifedipine (L-type calcium-channel blocker), ruthenium red, ryanodine (blockers of inositol 1,4,5-trisphosphate-insensitive calcium stores), or 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC; phospholipase C inhibitor). Area under the contraction curve was analyzed, and pD2 (log of concentration yielding 50% of maximum response) values and maximum relaxation responses were calculated. The maximum relaxation response to nifedipine was increased in both longitudinal (P < 0.01) and circular (P < 0.05) myometrial layers from LTH compared to control tissue, whereas no difference was observed in response to ruthenium red or ryanodine. The maximum relaxation response to NCDC was lower in the LTH circular layer (P < 0.05). Together, these data are indicative of an increase in the dependence of ovine uterine smooth muscle on extracellular calcium influx through the L-type, voltage-gated calcium channels following LTH. This appears to occur not through an increase in L-type calcium channels but, rather, through a possible decline in importance of the oxytocin-induced, phospholipase C-mediated pathway, resulting in a greater proportion of extracellular calcium contributing to contraction. Layer-dependent differences also exist between the circular and longitudinal myometrium in response to phospholipase C inhibition.

1 Supported by NIH grant HD-31226.

2 Correspondence: Charles A. Ducsay, Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350. FAX: 909 558 4029; cducsay{at}som.llu.edu






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Copyright © 2004 by the Society for the Study of Reproduction.