The conscious instrumented rabbit: a model for the study of mechanisms of blood pressure regulation during pregnancy.

Abstract

SUMMARY Conscious pregnant and nonpregnant rabbits were used to further evaluate the role of prostaglandin (PG) and plasma renin activity (PRA) in the systemic hemodynamics of pregnancy. Pregnant rabbits had high peripheral blood levels of both PGE 2 and PRA. Systemic blood pressure was not affected in either pregnant or nonpregnant by the administration of an inhibitor of prostaglandin synthesis. Pregnant rabbits, however, had a much larger decrease in blood pressure than nonpregnant animals when given the angiotensin I (Al)-converting-enzyme inhibitor, captopril. Pregnant rabbits were more resistant to the pressor effect of exogenous All than nonpregnant animals. The pressor effect of All increased in pregnant rabbits after the administration of meclofenamate and parturition but was not changed by volume expansion. In contrast, the sensitivity of nonpregnant rabbits to AH increased after volume expansion, but not after treatment with inhibitors of prostaglandin synthesis. These studies demonstrate that a remarkable similarity exists between pregnant rabbits and pregnant women in the pressor response to AH. This study is the first to correlate the vasopressor response to AH with PRA and the level of a circulating vasopressor prostaglandin in pregnant animals. The results strongly suggest that this model will be fruitful in further attempts to define the factors controlling systemic hemodynamics during pregnancy. (Hypertension 5: S14- S2O, 1983)

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.…”

“…1 and 2 in Reference 50). The same inhibitor significantly decreased the dose of All required to raise diastolic pressure by 20 mmHg in pregnant rabbits, although the amount of All needed to achieve this rise in blood pressure was not significantly different from that in nonpregnant animals before meclofenamate was given (51). Mc-Laughlin and associates (64) demonstrated that the threshold concentration required to raise blood pressure by 4 mmHg was increased for All, but not for barium chloride in the perfused hind limb of pregnant rabbits.…”

“…(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.…”

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

“…Bay K 8644 (BAY), an L-VDCC agonist, was infused in pregnant and nonpregnant anesthetized rabbits (10,20,40, and 60 g/kg) and pregnant and nonpregnant conscious, chronically instrumented (conscious) rabbits (10,25, and 50 g/kg). BAY infusions resulted in greater elevation of mean arterial pressure in both anesthetized pregnant (n ϭ 6) vs. nonpregnant (n ϭ 6) (P Ͻ 0.05) and conscious pregnant (n ϭ 10) vs. nonpregnant (n ϭ 10) rabbits (P Ͻ 0.05).…”