Role of Nox1 on internal pudendal artery dysfunction in diabetic mice

• Grant number: 15/00832-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 01, 2015
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Rheure Alves Moreira Lopes
• Supervisor: Rhian M. Touyz
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Glasgow, Scotland
• Associated to the scholarship: 12/12178-6 - Involvement of NADPH oxidase in pudendal artery reactivity in diabetic mice, BP.DR

Abstract

Hyperglycemia, hyperlipidemia and inflammation, three main metabolic abnormalities in diabetes mellitus (DM), can induce ROS generation. NADPH oxidase has been identified as the main source of ROS in the vasculature. NOX1, a NADPH oxidase isoform, plays an important role in vascular smooth muscle cell (VSMC) proliferation, migration, and extracellular matrix production. Oxidative stress is known to be critically involved in the vascular complications associated with metabolic and cardiovascular diseases, including nephropathy, cardiomyopathy, endothelial dysfunction and erectile dysfunction. DM is an important risk factor for erectile dysfunction (ED), the inability to develop or maintain penile erection during sexual activity. The arterial blood flow to the corpus cavernosum originates from the internal iliac arteries, courses to the internal pudendal arteries (IPAs) and terminates in the bilateral cavernous arteries. Functional or structural changes in the IPAs can lead to ED. We hypothesized that diabetes-induced increased ROS generation, consequent to increased activation of NOX1, impairs IPAs function. Type 1 DM will be induced in C57BL6 and NOX1 KO (knockout) mice by using streptozotocin (STZ). Vascular function will be determined in IPAs mounted in a wire myograph, ROS generation by lucigenin, amplex red and HPF (Hydroxyl Radical and Peroxynitrite Sensor), NO by DAF-FM diacetate and gene expression by real time PCR in VSMC from IPAs. ML171, a NOX1 inhibitor will be used in IPAs and cultured VSMC to determine whether activation of NOX1 leads to IPAs dysfunction. (AU)