Blood pressure control in pregnant rabbits: norepinephrine and prostaglandin interactions

Abstract

The relationship between norepinephrine (NE) and prostaglandins in the regulation of systemic blood pressure during pregnancy was examined in conscious rabbits. The arterial prostaglandin E2 (PGE2) concentration was higher in pregnant than in nonpregnant rabbits. Resting blood pressure was slightly lower in the gravid animals. The pressor response to incremental doses of intravenous NE was blunted in the pregnant rabbits. Meclofenamate, a cyclooxygenase inhibitor, failed to alter the resting blood pressure in either group of animals, although it reduced PGE2 levels more than 60% in the pregnant rabbits. The pressor response to NE was significantly increased only in the pregnant rabbits when the NE infusion was repeated following meclofenamate. Pregnant rabbits could also be differentiated from nonpregnant by their higher peripheral blood levels of NE and their uniform hypotensive response to alpha-adrenergic blockade. These observations define an altered responsiveness to both endogenous and exogenous NE in pregnant rabbits that appears to be related to an increase in vasodilator prostaglandins.

Evidence against the hypothesis that prostaglandins are the vasodepressor agents of pregnancy. Serial studies in chronically instrumented, conscious rats.

“…Indomethacin may promote antikaliuresis indirectly, by inhibition of the renin-angiotensin aldosterone axis (37). The attenuated systemic pressor response to exogenous vasoconstrictors that develops during pregnancy has been observed in many species (26,(47)(48)(49)(50)(51)(52), present study). The mechanism(s) is not clearly defined, and prereceptor, receptor, and/or postreceptor phenomena could contribute.…”

“…Hart (65,66) has shown that aortic arterial and portal venous strips from pregnant rats display a reduction in barium-induced increments of tension. These studies (50,51,(64)(65)(66), including our own, perhaps suggest that pressor responsiveness in pregnant rabbits and rats are modified by different mechanisms.…”

“…(The above discussion of All and NE applies to arginine vasopressin, which Paller also used to elicit pressor responses.) Venuto and colleagues have provided the most convincing data that PGs modify the pressor response during pregnancy, at least in rabbits (50,51). Meclofenamate was given acutely to conscious, pregnant rabbits (48-72 h were allowed for recovery from surgery), and partial restoration of the pressor response to NE was observed (compare their Figs.…”

Lack of beneficial effects of the NO‐donor, molsidomine, in the L‐NAME‐induced pre‐eclamptic syndrome in pregnant rats

“…It should however be stressed that the vasopressor responses achieved in our L-NAME-treated pregnant rats always remained smaller than those obtained in untreated non pregnant rats and that, in another study, vascular refractoriness to phenylephrine was not suppressed at all after L-NAME (Nathan et al, 1995). Thus, if NO appears to play an important role in the development of reduced vascular reactivity during pregnancy, other factors are probably also involved, e.g., vasodilator prostaglandins (Venuto et al, 1984), oestrogens (Shan et al, 1994), etc . .…”

Enhanced vascular effects of the Ca2+channel agonist Bay K 8644 in pregnant rabbits

“…ACUTELY STUDIED RABBITS: The protocol followed was described previously in similar studies (37). Briefly, general anesthesia was achieved with intravenous pentobarbital sodium (30 mg/kg).…”