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Consequences of chronic ethanol consumption on metalloproteinases and MAPKs pathways and tissue remodeling in the corpus cavernosum of rats.

Grant number: 12/04144-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2012
Effective date (End): July 31, 2015
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Carlos Renato Tirapelli
Grantee:Jaqueline Jóice Muniz
Home Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Chronic ethanol consumption is one of the risk factors for erectile dysfunction (ED) of vascular origin, which impairs erection and can lead to other vascular diseases. Erection consists on a mechanism involving nervous stimulation, vasoconstrictors and vasodilators substances. Nitric oxide (NO) is an important vasodilator agent, which induces relaxation of smooth muscle cells of the cavernous tissue allowing increased penile blood flow and erection. Among the vasoconstrictors substances which control the cavernosum muscle tone, the most important are noradrenaline and endothelin-1 (ET-1). These vasoconstrictors difficult blood flow to the penis, keeping it in its flaccid state, in other words, non-erect. Chronic ethanol consumption increases the contraction induced by ET-1 in the rats' corpus cavernosum, as seen on our pilot study results. It is known that in addition to its effects on vasoconstriction, ET-1 activates other intracellular pathways, such as the mitogen-activated protein kinases (MAPKs), metalloproteinases (MMPs), and increases production of reactive oxygen species (ROS). In some tissues it has been shown that activation of these pathways leads to increased vascular contraction, cell proliferation, and remodeling. However, it is unclear whether stimulation of the endothelinergic system by ethanol can lead to activation of these pathways in the cavernous tissue. Since chronic ethanol consumption increases the reactivity of rat corpus cavernosum to ET-1, our hypothesis is that this endothelinergic activation leads to stimulation of MAPKs and MMPs pathways, ROS generation, causing structural and functional alterations in cavernous tissue. Thus, the aim of this study is to evaluate the consequences of this activation on the expression and actions of MAPKs, MMPS, tissue remodeling and ROS production in the rats' corpus cavernosum.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MUNIZ, JAQUELINE J.; LEITE, LETICIA N.; DE MARTINIS, BRUNO S.; CARNEIRO, FERNANDO S.; TIRAPELLI, CARLOS R.. Chronic ethanol consumption induces erectile dysfunction: Role of oxidative stress. Life Sciences, v. 141, p. 44-53, . (12/04144-4, 11/12911-2)
MUNIZ, JAQUELINE J.; LEITE, LETICIA N.; LACCHINI, RICCARDO; TANUS-SANTOS, JOSE E.; TIRAPELLI, CARLOS R.. Dysregulated mitogen-activated protein kinase and matrix metalloproteinase in ethanol-induced cavernosal dysfunction. Canadian Journal of Physiology and Pharmacology, v. 96, n. 3, . (12/04144-4, 11/12911-2)

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