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Consequences of chronic ethanol consumption on the reactivity and expression of components of the endothelinergic system in the rat corpus cavernosum

Grant number: 11/12911-2
Support Opportunities:Regular Research Grants
Duration: October 01, 2011 - September 30, 2013
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Carlos Renato Tirapelli
Grantee:Carlos Renato Tirapelli
Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers:Ana Maria de Oliveira ; Jose Eduardo Tanus dos Santos


The balance between contractile and dilator factors determines the erectile tissue smooth muscle tone in the sinusoidal spaces of the cavernous body, as in the spiral arteries and arterioles of penile resistance, which in turn determines the inflow of blood into the penis and the consequent increase in intra-penile pressure necessary for penile erection process. Endothelin-1 (ET-1) is a vasoconstrictor peptide that plays an important role in controlling the tone of the cavernous body. However, it has been demonstrated that this peptide is also involved in erectile dysfunction (ED) associated with diabetes mellitus and hypertension. Several studies show that chronic consumption of ethanol is considered a risk factor for ED. Ethanol consumption increases plasma levels of ET-1 and the contractile response to this peptide in vascular tissues. Moreover, ethanol consumption induces endothelial dysfunction by a process that involves the production of reactive oxygen species (ROS) and reduced bioavailability of nitric oxide (NO). Although some studies describes that chronic consumption of ethanol leads to increased blood pressure, changes in vascular responses to vasoactive agents and release of substances that control vascular function, there are no reports on the effect of chronic ingestion of ethanol on the endothelinergic system in corpus cavernosum. Therefore, it becomes pertinent to study the cellular and functional consequences of chronic consumption of ethanol on the endothelinergic system in penile circulation as well as the mediators involved in this response. The hypotheses of this study are that chronic ethanol consumption 1) increases the reactivity of corpus cavernosum to ET-1; 2) stimulates the penile endothelinergic system which, in turn, induces the activation of signaling pathways such as MAPKs and metalloproteinases (MMPs); 3) increases the generation of ROS (via NADPH oxidase) with consequent reduction in the bioavailability of NO. (AU)

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Scientific publications (5)
(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.; 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)
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)
L.N. LEITE; N.A. GONZAGA; D.P.C. TIRAPELLI; L.F. TIRAPELLI; C.R. TIRAPELLI. Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle. Brazilian Journal of Medical and Biological Research, v. 47, n. 10, p. 876-885, . (11/12911-2)
PASSAGLIA, PATRICIA; GONZAGA, NATALIA A.; TIRAPELLI, DANIELA P. C.; TIRAPELLI, LUIS F.; TIRAPELLI, CARLOS R.. Pharmacological characterisation of the mechanisms underlying the relaxant effect of adrenomedullin in the rat carotid artery. Journal of Pharmacy and Pharmacology, v. 66, n. 12, p. 1734-1746, . (11/12911-2)
LEITE, LETICIA N.; LACCHINI, RICCARDO; CARNIO, EVELIN C.; QUEIROZ, REGINA H.; TANUS-SANTOS, JOSE EDUARDO; DE OLIVEIRA, ANA M.; TIRAPELLI, CARLOS R.. Ethanol Consumption Increases Endothelin-1 Expression and Reactivity in the Rat Cavernosal Smooth Muscle. ALCOHOL AND ALCOHOLISM, v. 48, n. 6, p. 657-666, . (11/12911-2)

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