Requirement for Ca2+ mobilization and increased prostaglandin production for maximal decidualization in rats and the involvement of angiotensin II.
Studies were performed to determine whether the inhibition of the decidual cell reaction induced by intrauterine infusion of the angiotensin converting enzyme inhibitor enalaprilat in rats is reversed by activation of Ca2+ influx. Influx of Ca2+ was shown to be stimulated by angiotensin II in endometrial cells in this study. Ovariectomized, adult female rats were sensitized for the decidual cell reaction with steroid treatments. For experiments in vivo, intrauterine infusions of enalaprilat alone, or in combination with the Ca2+ ionophore A23187, a synthetic diacylglycerol, and dioctanoyl-sn-glycerol (diC8), and PGE2 were initiated on the day of uterine sensitivity. Enalaprilat inhibited the increases in uterine PG concentrations and uterine weight that occur following infusion of the vehicle. Concurrent infusion of A23187 partially, but not completely, reversed the inhibition of uterine weight increase; diC8 did not affect the inhibition of enalaprilat. A23187 did not reverse the effects of enalaprilat on uterine PG concentrations. Concurrent infusion of A23187 and PGE2 fully reversed the inhibitory effect of enalaprilat on uterine weight. For experiments in vitro, endometrial stromal and epithelial cells were obtained from uteri on the day of sensitivity and maintained in suspension. Cytosolic free calcium concentration ([Ca2+]i) was monitored in cell suspensions by fluorescence spectrophotometry using the Ca(2+)-sensitive probe, indo-1. Angiotensin II induced a transient increase in [Ca2+]i of endometrial stromal cell suspensions, but not of epithelial cells; PGE2 did not increase [Ca2+]i in stromal or epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Squires
P M
PM
Department of Physiology, University of Western Ontario, London, Canada.
Dixon
S J
SJ
Kennedy
T G
TG
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D003656:Decidua / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012504:Saralasin / Q000494:pharmacology; D014599:Uterus / Q000033:anatomy & histology
D011453:Prostaglandins; D000804:Angiotensin II; D000001:Calcimycin; D015773:Enalaprilat; D012504:Saralasin; D015232:Dinoprostone; D002118:Calcium