TP receptors mediate ROS generation and enhanced contractions to endothelin‐1 in mesenteric arterioles from angiotensin II infused mice

We reported that thromboxane‐prostanoid receptors (TPRs) mediated hypertension in Ang II infused mice. Since hypertension depended on O 2 •− , we hypothesised that TP‐Rs mediate vascular O 2 •− . TP‐R+/+ and −/− mice were infused with Ang II or vehicle (v) for 14 days and mesenteric arterioles (MAs) studied in a wire myograph with vascular O 2 •− quantitated from ethidium:dihydroethidium (E/D). Ang II infusion did not modify contraction of MAs to phenylephrine, but enhanced contractions to ET‐1 in TP‐R +/+ (122±5 vs 94±4%; p<0.01) but not TP‐R −/− mice (96± 3 vs 93±7%;). ET‐1 increased the E/D ratio of TP‐R +/+ MAs from Ang II but not V mice (3.2 ±0.3 vs 0.2±0.05; p<0.05). ET‐1 did not generate ethidium in TP‐R−/− MAs. The increased contractions to ET‐1 in TP‐R +/+ mice infused with Ang II were significantly (p<0.05) diminished by incubation of MAs with antagonists of COX‐1(SC560), −2 (paracoxib), TxA 2 synthase (OKY‐046) or 19,20‐HETE (APK‐II‐707) or by an SOD mimetic (tempol) but none altered responses in TR‐R−/− MAs. In conclusion, a slow pressor infusion of Ang II enhanced vascular ET‐1 contractions via O 2 •− , HETE and a COX product. Remarkably, both the enhanced contractions and the O 2 •− generation depended on TP‐Rs.