RELATIVE CONTRIBUTIONS OF ERα AND ERβ TO REGULATION OF CONSTRICTOR PROSTANOID (CP) FUNCTION IN FEMALE RAT AORTA

Abstract

Previously, we reported that estrogen enhances CP-potentiated vascular contraction by upregulating expression of COX-2 and thromboxane (TX) synthase. Therefore, the relative roles of estrogen receptor subtypes ERα and ERβ in CP function in female rat aorta were determined. Sprague-Dawley rats were ovariectomized (OvX) or OvX + treated with ER-selective agonists 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN, ERβ) or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, ERα), 100 μg/rat/day, 13-16 days). Paired thoracic aortic rings were prepared for isometric tension recording using standard methods, and were pretreated with SQ 29,548 (SQ, 1 μM) or control, and a concentration-response to arginine vasopressin (VP) obtained (10−11−10−6 M). VP-stimulated TX release was measured by RIA of TXB2. Data are means ± S.E. (n = 4 rats/group). Maximal response to VP in OvX (2,485±394 mg/mg ring wt) was unaffected by SQ. PPT enhanced maximal response to VP (4,079±361 mg), which was attenuated by SQ (2,734±429 mg). In contrast, DPN did not alter response to VP (2,187±680) and SQ had no effect. VP-stimulated TX release was similar in PPT (201±23 pg/mg tissue/45 min) and DPN (189±17 pg) but markedly lower in OvX (38±4 pg). In previous studies, 17β-estradiol replacement of OvX rats enhanced aortic response to VP (5,058±193 mg), and restored the attenuating effect of SQ (3,471±206 mg), and increased TX release (91±10 pg). These data suggest that ERα but not ERβ is important in the effect of estrogen to enhance CP-potentiated vascular contraction in female rat aorta. (Supported by TAMU-LSTF).