Key result
Flurbiprofen increases basal BP and enhances angiotensin II pressor response, while PGE1 shows biphasic effects.
Why the study?
Does prostaglandin inhibition or PGE1 infusion alter the pressor response to angiotensin II in pregnant rabbits?
Does prostaglandin inhibition or PGE1 infusion alter the pressor response to angiotensin II in pregnant rabbits?
Prostaglandins modulate the pressor response to angiotensin II in pregnant rabbits in a dose-dependent manner.
Answers are grounded in this paper and cite their sources.
Should not change practice in human pregnancy; leaves open dose-dependent prostaglandin effects on angiotensin II responsiveness for further study.
A total of 24 rabbits between days 26–29 gestation (term 31 days) were studied acutely. Five does had been pretreated with oral doses (40 mg p.d.) of a prostaglandin synthetase inhibitor (Flurbiprofen) since day 7 of gestation. Rabbits were anaesthetised with sodium phenobarbitone, 30 mg kg−1, and breathed spontaneously. The pressor response to stepwise increments of infused angiotensin II (AII) over the range 16–64 ng kg−1 min−1 was determined in all animals. The 19 does which had not received Flurbiprofen were then subdivided into 4 groups, receiving infusions either of normal saline, 0.1 ml min−1 (n=6) or prostaglandin E1 (PGE1) at 10 ng kg−1 min (n=4), 20 ng kg−1 min (n=5) or 50 ng kg−1 min−1 (n=4). The infusions of AII were then repeated during the additional infusion.The administration of Flurbiprofen was associated with increased basal systolic and diastolic blood pressures. The doses of AII given evoked clear and consistent increases in both systolic and diastolic blood pressure. The previous administration of Flurbiprofen was associated with a consistently greater pressor response to AII than in the untreated does. Since the basal plasma renin concentration-was almost halved in these animals, the enhanced response may have been a function of circulating endogenous concentrations. Flurbiprofen had no effect on renal histology as sham by light or electron microscow.The additional infusion of PGE1 had a biphasic effect, dependent on administered dose, on the pressor response to AII. Thus PGE1 10 ng kg−1 min−1 was associated with a blunting of response to AII, while PGE1 50 ng kg−1 min−1 was associated with an enhanced response. A similar dose dependent biphasic effect has been reported in isolated segments of vascular tissue.
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Sheehan et al. (1983) studied Pregnancy (n=24). Flurbiprofen and Prostaglandin E1 (PGE1) vs. Untreated does / normal saline was evaluated on Pressor response to stepwise increments of infused angiotensin II. Flurbiprofen increased basal blood pressure and enhanced the pressor response to angiotensin II, while PGE1 had a biphasic dose-dependent effect on the pressor response.
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