Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

• DOI: 10.1371/journal.pone.0036027
• Publication Date: 2012-04-23T21:37:15Z
• Authors: Ana Sánchez; Cristina Contreras; María Pilar Martínez; Belén Climent; Sara Benedito; Albino García-Sac...; Medardo Hernández; Dolores Prieto
• Keywords: Dysfunctional family

Objective Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural involving nitric oxide (NO) are usually implicated the pathophysiology diabetic ED, but underlying mechanisms unclear. The present study assessed role oxidative stress dysfunctional vasodilator responses penile arteries obese Zucker rat (OZR), experimental model metabolic syndrome/prediabetes. Methods Results Electrical field stimulation (EFS) under non-adrenergic non-cholinergic (NANC) conditions evoked relaxations that were significantly reduced OZR compared those lean rats (LZR). Blockade NO synthase (NOS) inhibited both LZR OZR, while saturating concentrations NOS substrate L-arginine reversed inhibition restored levels from LZR. nNOS expression was unchanged selective decreased EFS not endothelium removal did alter these either strain. Superoxide anion production nitro-tyrosine immunostaining elevated erectile tissue OZR. Treatment NADPH oxidase inhibitor apocynin or acute incubation cofactor tetrahydrobiopterin (BH4) control arteries, enzyme BH4 synthesis GTP-cyclohydrolase (GCH) donor SNAP induced decreases intracellular calcium impaired controls. Conclusions demonstrates nitrergic signalling uncoupling insulin resistance. This likely contributes syndrome-associated along endothelial also altered signalling.