Selective Estrogen Receptor Agonists Enhance Blood Pressure, Thromboxane and Prostacyclin in Aortic Coarctation‐Induced Hypertensive Female Rats

Abstract

Previously, we reported that estrogen receptors (ERα, ERβ) exert differing effects on mesenteric arterial reactivity to vasopressin (VP) and that estrogen enhances constrictor prostanoids by upregulating thromboxane synthase and cyclooxygenase‐2 message in rat aorta. We measured mean arterial blood pressure (BP), thromboxane (TXA2) and prostacyclin (PGI2) release by mesenteric arterioles (200 μm) in normo‐ and aortic coarctation‐induced hypertensive (NT and HT) Sprague‐Dawley female rats that were intact (INT), ovariectomized (OvX), or OvX + treated with ER‐selective agonists DPN (ERβ) or PPT (ERα), 100μg/rat/day (13–15 days). BP in PPT HT (180±4 mmHg) is similar to INT HT (183±4) and DPN HT (182±4). BP is lowest in OVX HT (153±3). BP in NT did not differ (mean = 127±1). Basal TXA2 was lowest in OVX and DPN NT (51 ± 20; 40 ± 7 pg/mg tissue/45 min), while INT or PPT NT are higher (93 ± 1; 93 ± 10). HT increases basal TXA2 threefold. VP (10−8) increases TXA2 least in DPN NT (79 ± 11) vs INT NT (108 ± 1), OVX NT (137 ± 33) or PPT NT (134 ± 31). HT increases VP stimulated TXA2. PPT HT increased the most (643 ± 137) vs INT HT (415 ± 46), OVX HT (277 ± 56) or DPN HT (334 ± 33). PGI2 shows similar trends in all groups; PPT enhanced basal and VP stimulated PGI2 the most. These data suggest that ERα enhances TXA2 and PGI2 to a greater extent than ERβ. The increased PGI2 does not afford protection to BP in PPT HT. (Supported by NIH: HL‐080402)