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Articles in PresS, published online ahead of print November 27, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00523.2002
Submitted on August 29, 2002
Accepted on November 21, 2002
1 Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
* To whom correspondence should be addressed. E-mail: hmertz{at}hsc.wvu.edu.
The importance of prostaglandins in the regulation of the renin-angiotensin system during development is not known. These experiments were conducted to examine the effects of prostaglandin synthesis inhibitors on basal and isoproterenol induced plasma renin concentration and renin gene expression in the late gestation fetal lamb. Eighteen lamb fetuses ranging in gestational age from 129-138 days underwent surgical insertion of femoral arterial and venous catheters under general endotracheal anesthesia. After a period of recovery, animals underwent an infusion of isoproterenol after administration of a saline bolus (control experiments). 24-48 hours later a second study was performed after administration of NS-398, a cyclooxygenase-2 inhibitor, or saline for a second control study. Administration of COX-2 inhibitor significantly reduced baseline plasma renin levels and attenuated responses in fetal renin secretion to isoproterenol infusions. Renal cortical cells from animals receiving COX-2 inhibitor had significantly lower levels of renin mRNA as compared to animals receiving only saline. Renal cortical cells in culture from animal receiving only saline exhibited increased levels of renin mRNA when treated with isoproterenol, forskolin, or isobutyl methylxanthine. Only forskolin increased renin mRNA levels in renal cortical cells in culture from animals receiving COX-2 inhibitor. We conclude that prostaglandins play a stimulatory role in the regulation of the renin-angiotensin system and are necessary for beta-adrenergic stimulation of renin secretion and gene expression in the late gestation fetal lamb.
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