Angiotensin II constriction of rat vasa recta is partially thromboxane dependent

We tested the hypothesis that thromboxane generation mediates vasoconstriction of isolated outer medullary descending vasa recta (OMDVR) by angiotensin (Ang) II. The lipoxygenase and cyclooxygenase (COX) inhibitor eicosatetraynoic acid (1 micromol/L) and the COX inhibitor indomethacin (1 micromol/L) partially reversed Ang II (1 nmol/L) constriction of in vitro perfused OMDVR. To determine whether thromboxane is a mediator of Ang II-induced vasoconstriction, a thromboxane synthase inhibitor, U63577A (1 micromol/L), and thromboxane receptor antagonists, SQ-29548 or BMS-180,291 (1 micromol/L, each), were introduced into the bath of vessels that had been preconstricted by Ang II (1 nmol/L). These agents significantly inhibited vasoconstriction induced by Ang II. In contrast, SQ-29548 and U63557A did not affect vessels preconstricted by raising extracellular KCl from 5 to 100 mmol/L. The thromboxane receptor agonist U46619 (1 micromol/L) constricted OMDVR, an effect that was blocked by the antagonist BMS-180,291. In separate protocols, microperfused OMDVR were pretreated with U63577A or SQ-29548, after which they were exposed to luminal Ang II to induce vasoconstriction. Both agents inhibited vasoconstriction whether preexposure to them was via the bath or the perfusate. We conclude that Ang II-induced constriction of OMDVR is partly mediated by metabolites of arachidonic acid, including thromboxanes.