TP receptors regulate renal hemodynamics during angiotensin II slow pressor response

We investigated the hypothesis that thromboxane A2 (TxA2)-prostaglandin H2 receptors (TP-Rs) mediate the hemodynamic responses and increase in reactive oxygen species (ROS) to ANG II (400 ng·kg−1·min−1 sc 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 TxB2 but increased NOx and paradoxically decreased RVR (−2.1 ± 1.7 vs. +2.6 ± 0.8 mmHg·ml−1·min−1·g−1). Blockade of AT1 receptor of TP −/− mice infused with ANG...