Estradiol increases angiotensin II type 1 receptor in hearts of ovariectomized rats.

We tested the hypothesis that 17beta-estradiol (E(2)) has dual effects on the heart, increasing levels of proteins thought to have beneficial cardiovascular effects (e.g. endothelial nitric oxide (NO) synthase (eNOS)) as well as those thought to have detrimental cardiovascular effects (e.g. type 1 angiotensin II (AngII) receptor (AT(1)R)). Ovariectomized Wistar rats consuming a high-sodium diet received one of four treatments (n=7 per group): group 1, placebo pellets; group 2, E(2) (0 x 5 mg/pellet, 21-day release); group 3, NOS inhibitor, N(omega)-nitro-L-arginine-methyl-ester (L-NAME; 40 mg/kg per day for 14 days) plus Ang II (0 x 225 mg/kg per day on days 11-14); group 4, E(2) plus L-NAME/Ang II. E(2) increased cardiac levels of estrogen receptors ESR1 and ESR2, an ESR-associated membrane protein caveolin-3, eNOS, and phosphorylated (p)eNOS, thus, exerting potentially beneficial cardiovascular effects on NO. However, E(2) also increased cardiac levels of proteins associated with cardiovascular injury and inflammation including, AT(1)R, protein kinase C delta (PRKCD), phosphorylated PRKC, and phosphorylated extracellular signal regulated kinase (pMAPK)3/1, plasminogen activator inhibitor-1 (PAI-1), osteopontin and ED-1, a monocyte/macrophage-specific protein. E(2) treatment led to similar protein changes in the hearts of L-NAME/Ang II-treated rats except that the increase in peNOS was prevented, and L-NAME/Ang II and E(2) had additive effects in increasing cardiac PRKCD and PAI-1. Thus, the highest levels of cardiac PAI-1 and PRKCD occurred in L-NAME/Ang II-treated rats receiving E(2). In summary, E(2) treatment increased cardiac expression of AT(1)R as well as the expression of pro-inflammatory and prothrombotic factors.