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 thromboxane A2 (TxA2) in the rat renal vasculature during hypertension. In vivo measurements of renal blood flow (RBF) were made in 6-wk-old anesthetized spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats pretreated with indomethacin. The stable TxA2 agonist U-46619 was injected into the renal artery, and the magnitude and the kinetic parameters of the renal response were evaluated before and after continuous intrarenal infusion of a low dose of PGE2, Viprostol (PGE2 analogue), PGI2, and iloprost (PGI2 analogue). The selected dose of vasodilator PGs did not affect arterial pressure and RBF. In the control period, the TxA2 agonist reduced RBF by 30% with a 90-s half time of recovery in both strains. Infusion of vasodilator PGs in young WKY significantly blunted the maximum vasoconstrictor effect of the TxA2 agonist and facilitated 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, infusion of bradykinin or dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cAMP) blunted the TxA2-induced vasoconstriction to a similar degree in both strains. These results indicate that vasodilator PGs attenuate the action of TxA2 by at least two mechanisms. One mechanism affects the size of the constrictor response and is probably related to cAMP levels, and the other influences the rate of the recovery from the vasoconstriction. The renal vasculature of young SHR exhibits a defect in the first mechanism. This impaired ability of vasodilator PGs to block the renal vasoconstriction induced by TxA2 could play an important role in the development of hypertension.