Calcium modulation of endothelium-derived prostacyclin production in ovine pregnancy

Ronald R. Magness, Charles R. Rosenfeld

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Refractoriness to angiotensin-II (ANG II)-induced vasoconstriction is greater in the uteroplacental us. systemic vascular beds during pregnancy, possibly reflecting enhanced uterine artery prostacyclin production. We determined the role(s) of calcium and calcium channels in regulating basal and ANG Il-induced vascular prostacyclin production in uterine and omental (systemic) arteries obtained from pregnant (P) and nonpregnant (NP) ewes. To evaluate the endothelial contribution to basal and stimulated prostacyclin production, arteries with and without endothelium also were incubated in the absence and presence of 50 nM ANG II, 5 μM A23187, or 5 μM arachidonate. Basal prostacyclin production by intact and denuded uterine and systemic arteries was P > NP (P < 0.05), plus in intact arteries, production fell -33% in calcium-free Krebs-Henseleit and 5 EGTA. Although basal prostacyclin production by P and NP uterine and NP systemic arteries was unaffected by 5 μM verapamil, P systemic artery synthesis fell 41% (P < 0.05). P uterine artery prostacyclin production increased similarly with ANG II (61%) and A23187 (78%) in the presence of calcium (2 mM), whereas NP uterine arteries responded only to A23187 (71%). Verapamil inhibited ANG Il-induced increases in prostacyclin synthesis by P uterine arteries. Neither calcium removal nor verapamil altered prostacyclin responses to arachidonate (5 μM). The endothelium accounted for -68% of basal prostacyclin production by all arteries studied and for 100% of ANG Il-induced increases by P uterine arteries (P < 0.01). A23187 and arachidonate increased both endothelial and smooth muscle prostacyclin production (P < 0.01). During ovine pregnancy, extracellular calcium entry via activation of potential-gated calcium channels are involved in modulating basal vascular prostacyclin production as well as ANG Il-induced increases in uterine artery production. Furthermore, the endothelium is the primary source of basal vascular prostacyclin synthesis and the sole source of ANG II-stimulated increases by uterine arteries during pregnancy.

Original languageEnglish (US)
Pages (from-to)2445-2452
Number of pages8
JournalEndocrinology
Volume132
Issue number6
DOIs
StatePublished - Jun 1993

ASJC Scopus subject areas

  • Endocrinology

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