Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA2/isoprostane production

Abstract

The relative contributions of vasoconstrictor and of dilator systems are balanced in health. The balance is reset in disease, often favoring a predominant role of vasoconstrictors, perhaps due to positive interactions between constrictor systems. For example, in hypertension, chronic high levels of angiotensin II (ANG II) stimulate the production of thromboxane (TxA2/PGH2) and/or isoprostane that activate constrictor thromboxane prostanoid (TP) receptors in the vasculature. The present study evaluated a modest concentration of ANG II administered acutely into the renal artery on urinary excretion of TxB2 and isoprostane and possible renal TP receptor activation that might amplify ANG II-induced renal vasoconstriction. TP receptors were blocked with SQ29548 coinfused with ANG II. Results were compared with a time control group of continuous ANG II infusion (40 ng·min−1·kg body wt−1) over 90 min. TP receptor antagonism during 30–60 min had no effect on the reduction in renal blood flow (RBF) produced by ANG II (15.8 ± 2.8 vs. 13.2 ± 4.9%) ( P > 0.6). Likewise, there was no difference between groups during ANG II-induced renal vasoconstriction between 60–90 min in presence or absence of TP receptor antagonist (RBF −8.6 ± 4.0 vs. −9.6 ± 4.5%) ( P > 0.8). Systemic arterial pressure was stable throughout, so RBF changes reflected localized changes in renal vascular resistance. Urinary excretion of TxB2 and isoprostane were nearly doubled by ANG II. The present data indicate that short-term intrarenal infusion of ANG II rapidly increases renal production of TxA2 but that the ANG II-induced renal vasoconstriction is independent of TP receptor activation during the initial 90 min of local challenge with ANG II.