Prostaglandin interactions with angiotensin, norepinephrine, and thromboxane in rat renal vasculature

Abstract

The objective of this study was to investigate the ability of the vasodilator prostaglandins E2 (PGE2) and I2 (PGI2) to interact with the vasoconstrictor action of angiotensin II (ANG II), norepinephrine (NE), and thromboxane A2 (TxA2) in the renal vasculature. In 12-wk-old anesthetized Munich-Wistar rats pretreated with indomethacin, renal blood flow (RBF) was measured during bolus injection of ANG II, NE, U-46619 (TxA2 agonist), PGE2, viprostol (PGE2 agonist), PGI2 or iloprost (PGI2 agonist) into the renal artery. Agents were injected separately and in a mixture of one constrictor with one dilator. ANG II, NE, and U-46619 induced large decreases in RBF, whereas PGs and their analogues produced slight, but significant, vasodilatation. To evaluate possible interactions in the vasomotor mechanisms between the dilators and the constrictors, curves of transient responses of separate injections were added (one constrictor plus one dilator) to create a predicted response of a mixture. NE exhibited additive effects with all PGs, as evidenced by the similarity of measured and predicted responses. In contrast, the TxA2 agonist interacted in a nonlinear fashion with all PGs; the measured maximum vasoconstriction was less than that predicted, and all kinetic parameters for the measured response were shorter than those predicted. The measured response to mixtures of ANG II and all PGs had a faster recovery than that predicted. We propose that the similarity between measured and predicted responses is due to independent actions of these agents via distinct mechanisms. In contrast, nonadditive responses suggest that the mechanisms mediating vasomotor effects of these agents interact in some cellular event.