Involvement of NADPH oxidase in pudendal artery reactivity in diabetic mice

• Grant number: 12/12178-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2012
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Rheure Alves Moreira Lopes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 15/00832-1 - Role of Nox1 on internal pudendal artery dysfunction in diabetic mice, BE.EP.DR

Abstract

In healthy individuals, penile erection depends on highly coordinated responses that almost simultaneously involve relaxation of the pre-penile vasculature, as well as vessels and intra-penile smooth muscle. This triggers an increase in penile blood flow, increased intracavernosal pressure and the consequent tumescence. The internal pudendal arteries (IPAs) are responsible for about 70% of the resistance to blood flow going to the corpus cavernosum. Thus, several diseases that lead to increased resistance of IPAs as occlusion, stenosis, and atherosclerosis are associated with erectile dysfunction (ED). It is widely accepted that diabetes mellitus (DM) is an important risk factor for ED. Experimental models of type I and II DM have endothelial dysfunction and a significant decrease in erectile response. It is possible that diabetes-associated vascular complications also occur in IPAs, which may reduce blood flow to the corpus cavernosum and, consequently, impair erectile function. Oxidative stress plays an important role in vascular complications of DM and ED. It is possible that vascular changes associated with oxidative stress, common in DM, also occur in IPAs. Accordingly, the present study will test the hypothesis that increased generation of ROS induced by NADPH oxidase activation in diabetic animals impairs the function of IPAs. To test our hypothesis, we will use the streptozotocin-induced diabetes model in C57BL/6J mice. ROS will be measured in vascular smooth muscle cells isolated from IPAs; vascular reactivity of IPAs in the DMT wire myograph system; protein expression by western blot; vessel structure analysis will be performed in DMT pressure myograph system and with hematoxylin-eosin; , and erectile function will be evaluated in vivo. This study offers a new approach for the investigation of the mechanisms that contribute to ED associated with DM, mainly due to the lack of studies evaluating IPAs dysfunction in animal models of DM.

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)

ALVES-LOPES, RHEURE; NEVES, KARLA B.; MONTEZANO, AUGUSTO C.; HARVEY, ADAM; CARNEIRO, FERNANDO S.; TOUYZ, RHIAN M.; TOSTES, RITA C.. Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase-Dependent Mechanisms. Hypertension, v. 68, n. 4, p. 1056-1064, OCT 2016. (12/12178-6, 13/08216-2)

LOPES, RHEURE A.; NEVES, KARLA B.; TOSTES, RITA C.; MONTEZANO, AUGUSTO C.; TOUYZ, RHIAN M.. Downregulation of Nuclear Factor Erythroid 2-Related Factor and Associated Antioxidant Genes Contributes to Redox-Sensitive Vascular Dysfunction in Hypertension. Hypertension, v. 66, n. 6, p. 1240-1250, DEC 2015. (12/12178-6)