VASCULAR INTERACTIONS OF PROSTAGLANDINS WITH THROMBOXANE IN KIDNEYS OF RATS DEVELOPING HYPERTENSION

We investigated the ability of the vasodilator prostaglandins E2 (PGE2 ) and I2 (PGI2) to counterbalance the vasoconstrictor action of thromb oxane A2 (TxA2) in the rat renal vasculature during hypertension. In v ivo measurements of renal blood flow (RBF) were made in 6-wk-old anest hetized spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats p retreated with indomethacin. The stable TxA2 agonist U-46619 was injec ted into the renal artery, and the magnitude and the kinetic parameter s of the renal response were evaluated before and after continuous int rarenal infusion of a low dose of PGE2, Viprostol (PGE2 analogue), PGI 2, and iloprost (PGI2 analogue). The selected dose of vasodilator PGs did not affect arterial pressure and RBF. In the control period, the T xA2 agonist reduced RBF by 30% with a 90-s half time of recovery in bo th strains. Infusion of vasodilator PGs in young WKY significantly blu nted the maximum vasoconstrictor effect of the TxA2 agonist and facili tated the recovery from vasoconstriction. In marked contrast, infusion of the vasodilator PGs in young SHR failed to affect the magnitude of the vasoconstrictor effect of the TxA2 agonist, although the recovery from vasoconstriction was facilitated as in WKY. On the other hand, i nfusion of bradykinin or dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cAMP) blunted the TxA2-induced vasoconstriction to a simil ar degree in both strains. These results indicate that vasodilator PGs attenuate the action of TxA2 by at least two mechanisms. One mechanis m affects the size of the constrictor response and is probably related to cAMP levels, and the other influences the rate of the recovery fro m the vasoconstriction. The renal vasculature of young SHR exhibits a defect in the first mechanism. This impaired ability of vasodilator PG s to block the renal vasoconstriction induced by TxA2 could play an im portant role in the development of hypertension.