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

摘要

We tested the hypothesis that 17β-estradiol (E2) 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 (Ang II) receptor (AT1R)). Ovariectomized (OVX) Wistar rats consuming a high sodium diet received one of four treatments (n = 7 per group): group 1; placebo pellets, group 2; E2 (0.5 mg/pellet, 21-day release), group 3; NO synthase inhibitor, N^ω-nitro-L-arginine-methyl-ester (L-NAME) (40 mg/kg/day for 14 days) plus Ang II (0.225 mg/kg/day on days 11–14), and group 4; E2 plus L-NAME/Ang II. E2 increased cardiac levels of estrogen receptor (ER)-α, ER-β, a ER-associated membrane protein caveolin-3, eNOS, and phosphorylated (p)eNOS, thus, exerting potentially beneficial cardiovascular effects on NO. However, E2 also increased cardiac levels of proteins associated with cardiovascular injury and inflammation including, AT1R, protein kinase C (PKC)δ, phosphorylated PKC and phosphorylated extracellular signal regulated kinase (pERK)1/2, plasminogen activator inhibitor-1 (PAI-1), osteopontin and ED-1, a monocyte/macrophage-specific protein. E2 treatment led to similar protein changes in hearts of L-NAME/AngII treated rats except that the increase in peNOS was prevented, and L-NAME/AngII and E2 had additive effects in increasing cardiac PKCδ and PAI-1. Thus, the highest levels of cardiac PAI-1 and PKCδ occurred in L-NAME/AngII treated rats receiving E2. In summary, E2 treatment increased cardiac expression of AT1R as well as the expression of pro-inflammatory and pro-thrombotic factors.