TP receptors regulate renal hemodynamics during angiotensin II slow pressor response

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Abstract
We investigated the hypothesis that thromboxane A2(TxA2)-prostaglandin H2receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to ANG II (400 ng·kg−1·min−1sc for 14 days) using TP-R knockout (TP −/−) and wild-type (+/+) mice. TP −/− had normal basal mean arterial blood pressure (MAP) and glomerular filtration rate but reduced renal blood flow and increased filtration fraction (FF) and renal vascular resistance (RVR) and markers of ROS (thiobarbituric acid-reactive substances and 8-isoprostane PGF2α) and nitric oxide (NOx). Infusion of ANG II into TP +/+ increased ROS and thromboxane B2(TxB2) and increased RVR and FF. ANG II infusion into TP −/− mice reduced ANG I and increased aldosterone but caused a blunted increase in MAP (TP −/−: +6 ± 2 vs. TP +/+: +15 ± 3 mmHg) and failed to increase FF, ROS, or TxB2but increased NOx and paradoxically decreased RVR (−2.1 ± 1.7 vs. +2.6 ± 0.8 mmHg·ml−1·min−1·g−1). Blockade of AT1receptor of TP −/− mice infused with ANG II reduced MAP (−8 mmHg) and aldosterone but did not change the RVR or ROS. In conclusion, during an ANG II slow pressor response, AT1receptors activate TP-Rs that generate ROS and prostaglandins but inhibit NO. TP-Rs mediate all of the increase in RVR and FF, part of the increase in MAP, but are not implicated in the suppression of ANG I or increase in aldosterone. TP −/− mice have a basal increase in RVR and FF associated with ROS.