Activation of estrogen receptor β-dependent nitric oxide signaling mediates the hypotensive effects of estrogen in the rostral ventrolateral medulla of anesthetized ratsReportar como inadecuado




Activation of estrogen receptor β-dependent nitric oxide signaling mediates the hypotensive effects of estrogen in the rostral ventrolateral medulla of anesthetized rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Biomedical Science

, 16:60

First Online: 07 July 2009Received: 16 May 2009Accepted: 07 July 2009DOI: 10.1186-1423-0127-16-60

Cite this article as: Shih, CD. J Biomed Sci 2009 16: 60. doi:10.1186-1423-0127-16-60

Abstract

BackgroundApart from their well-known peripheral cardiovascular effects, emerging evidence indicates that estrogen acts as a modulator in the brain to regulate cardiovascular functions. The underlying mechanisms of estrogen in central cardiovascular regulation, however, are poorly understood. The present study investigated the cardiovascular effects of 17β-estradiol E2β in the rostral ventrolateral medulla RVLM, where sympathetic premotor neurons are located, and delineated the engagement of nitric oxide NO in E2β-induced cardiovascular responses.

MethodsIn male Sprague-Dawley rats maintained under propofol anesthesia, the changes of blood pressure, heart rate and sympathetic vasomotor tone after microinjection bilaterally into the RVLM of a synthetic estrogen, E2β were examined for at least 120 min. The involvement of ERα and-or ERβ subtypes was determined by microinjection of selective ERα or ERβ agonist into bilateral RVLM. Different NO synthase NOS inhibitors were used to evaluate the involvement of differential of NOS isoforms in the cardiovascular effects of E2β.

ResultsBilateral microinjection of E2β 0.5, 1, or 5 pmol into the RVLM dose-dependently decreased systemic arterial pressure SAP and the power density of the vasomotor components of SAP signals, our experimental index for sympathetic neurogenic vasomotor tone. These cardiovascular depressive effects of E2β 1 pmol were abolished by co-injection of ER antagonist ICI 182780 0.25 or 0.5 pmol, but not a transcription inhibitor actinomycin D 10 nmol. Like E2β, microinjection bilaterally into the RVLM of a selective ERβ agonist 2,3-bis4-hydroxyphenyl propionitrile DPN, 1, 2, or 5 pmol induced significant decreases in these hemodynamic parameters in a dose-dependent manner. In contrast, the selective ERα agonist 1,3,5-tris4-hydroxyphenyl-4-propyl-1H-pyrazole 5 pmol did not influence the same cardiovascular parameters. Co-administration bilaterally into the RVLM of NOS inhibitor N-nitro-L-arginine methyl ester 5 nmol or selective inducible NOS iNOS inhibitor S-methylisothiourea 25 pmol, but not selective neuronal NOS inhibitor 7-nitroindazole 0.5 pmol or endothelial NOS inhibitor N5-1-Iminoethyl-L-ornithine 2.5 pmol, significantly attenuated the cardiovascular depressive effects elicited by DPN 2 pmol.

ConclusionOur results indicate that E2β in the RVLM elicited short-term cardiovascular depressive effects via an ERβ-dependent nontranscriptional mechanism. These vasodepressor effects of E2β are likely to be mediated by the iNOS-derived NO in the RVLM.

Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-16-60 contains supplementary material, which is available to authorized users.

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Autor: Cheng-Dean Shih

Fuente: https://link.springer.com/







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