Estrogen in the paraventricular nucleus attenuates L-glutamate-induced increases in mean arterial pressure through estrogen receptor beta and NO.
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) beta mediates the effect of E2, because activation of ERbeta with diarylpropionitrile (50 pmol) attenuated the response by 57%, whereas activation of ERalpha with propyl-pyrazole-triol (20 pmol) had no effect. Furthermore, inhibition of ERbeta with R,R-tetrahydrochrysene (50 pmol) blocked the effect of E2, but inhibition of ERalpha 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 gamma-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 ERbeta, NO produced by neuronal NO synthase and eNOS, and partly by gamma-aminobutyric acid.
Gingerich
Sarah
S
Center for Neuroscience and Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Krukoff
Teresa L
TL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002317:Cardiovascular Agents / Q000008:administration & dosage; D047629:Estrogen Receptor beta / Q000502:physiology; D004967:Estrogens / Q000008:administration & dosage*; D018698:Glutamic Acid / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007267:Injections; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002317:Cardiovascular Agents; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid