Estrogen in the Paraventricular Nucleus Attenuates l -Glutamate–Induced Increases in Mean Arterial Pressure Through Estrogen Receptor β and NO

Abstract

Estrogen (E2) acts in the brain to decrease blood pressure (BP) responses to psychological stress. A likely site for the effects of E2 is the hypothalamic paraventricular nucleus (PVN), an important regulator of autonomic functions. We studied the effects of E2 in the PVN on BP and heart rate (HR) responses to l -glutamate injections into the PVN of male urethane-anesthetized rats. Microinjections of l -glutamate (50 nmol) into the PVN increased BP by 14±2.5 mm Hg and HR by 30±5.6 bpm. Microinjections of E2 (0.1, 1, and 10 pmol) into the PVN 30 minutes before l -glutamate dose-dependently attenuated the pressor response by 25%, 34%, and 59%, respectively, but did not affect HR. We determined that E2 receptor (ER) β mediates the effect of E2, because activation of ERβ with diarylpropionitrile (50 pmol) attenuated the response by 57%, whereas activation of ERα with propyl-pyrazole-triol (20 pmol) had no effect. Furthermore, inhibition of ERβ with R,R-tetrahydrochrysene (50 pmol) blocked the effect of E2, but inhibition of ERα with methyl-piperidino-pyrazole (1 nmol) did not. Finally, we found that the effect of E2 is mediated by NO, because the NO synthase (NOS) inhibitor, N G -nitro- l -arginine methyl ester (2 nmol), the neuronal NOS inhibitor, 7-nitroindazole sodium salt (0.1 pmol), and the endothelial NOS inhibitor, N5-(1-iminoethyl)- l -ornithine (200 pmol) blocked the effect of E2. The effect was partially blocked with the γ-aminobutyric acid A receptor inhibitor bicuculline. Our results demonstrate that E2 in the PVN attenuates the l -glutamate–induced pressor response and that this effect is mediated by ERβ, NO produced by neuronal NO synthase and eNOS, and partly by γ-aminobutyric acid.