PREGNANCY ENHANCES THE PRESSOR-RESPONSE TO THROMBOXANE ANALOGS IN RABBITS

In this study, we first tested the hypothesis that the previously demo nstrated circulatory failure and thrombocytopenia induced by intracava l administration of thromboxane A(2) (TxA(2)) analogues in nonpregnant (NP) rabbits [G. Losonczy, I. Mucha, J. DiPirro, J. Sweeney, G. Brown , J. Brentjens, and R. Venuto. Am. J. Physiol. 265 (Regulatory Integra tive Comp. Physiol. 34): R772-R780, 1993] could he avoided if the comp ounds were given instead into the aortic arch. Conscious New Zealand W hite rabbits received bolus injections of U-46619 (5-20 mu g) through a previously implanted catheter threaded into the aortic arch. Indeed, mean arterial pressure (MAP) rose modestly, and thrombocytopenia did not develop. Next, we compared the blood pressure responses of pregnan t (P) rabbits with those of NP rabbits to intra-aortic U-46619 and I-B OP, because they had been found to be resistant to both the hypotensiv e and platelet aggregatory effects of intracaval U-46619. Resting bloo d pressure was lower in P than in NP rabbits (74 +/- 3 vs. 95 +/- 2 mm Hg), but showed a greater increase in response to U-46619. For example , following a 20-mu g dose blood pressure rose 20 +/- 0.3 mmHg in P vs . 12 +/- 2.1 mmHg in NP rabbits (P < 0.02). Similar results were obtai ned with the second TxA(2) analogue I-BOP. Pregnancy-induced enhanceme nt of blood pressure elevation may be the consequence of peripheral va soconstriction, which was not seen in NP rabbits. Thus the actions of TxA(2) analogues U-46619 and I-BOP are markedly influenced by the rout e of administration. Furthermore, these compounds appear to be the onl y known vasoconstrictors whose prohypertensive effects are enhanced by normal pregnancy.