This Article Full Text Full Text (PDF) All Versions of this Article: 48/6/1130    most recent 01.HYP.0000248754.67128.ffv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gingerich, S. Articles by Krukoff, T. L. Search for Related Content PubMed PubMed Citation Articles by Gingerich, S. Articles by Krukoff, T. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE NITRIC OXIDE Related Collections Cardiovascular Pharmacology Cell signalling/signal transduction Hypertension - basic studies Endothelium/vascular type/nitric oxide

(Hypertension. 2006;48:1130.)
© 2006 American Heart Association, Inc.

Original Articles

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

From the Center for Neuroscience and Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Correspondence to Teresa L. Krukoff, Centre for Neuroscience and Department of Cell Biology, 5-31 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. E-mail teresa.krukoff{at}ualberta.ca

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) ß mediates the effect of E2, because activation of ERß with diarylpropionitrile (50 pmol) attenuated the response by 57%, whereas activation of ER with propyl-pyrazole-triol (20 pmol) had no effect. Furthermore, inhibition of ERß with R,R-tetrahydrochrysene (50 pmol) blocked the effect of E2, but inhibition of ER 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 -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 ERß, NO produced by neuronal NO synthase and eNOS, and partly by -aminobutyric acid.

Key Words: 17ß-estradiol • blood pressure • estrogen receptor • nitric oxide synthase • autonomic nervous system

This article has been cited by other articles:

				B. Xue, D. Badaue-Passos Jr, F. Guo, C. E. Gomez-Sanchez, M. Hay, and A. K. Johnson Sex differences and central protective effect of 17{beta}-estradiol in the development of aldosterone/NaCl-induced hypertension Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1577 - H1585. [Abstract] [Full Text] [PDF]

				B. Xue, Y. Zhao, A. K. Johnson, and M. Hay Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1025 - H1032. [Abstract] [Full Text] [PDF]

				C. M. Klinge, N. S. Wickramasinghe, M. M. Ivanova, and S. M. Dougherty Resveratrol stimulates nitric oxide production by increasing estrogen receptor {alpha}-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells FASEB J, July 1, 2008; 22(7): 2185 - 2197. [Abstract] [Full Text] [PDF]