Caracterização da disfunção erétil em camundongos obesos tratados com dieta hiperlipídica / Characterization of erectile dysfunction in obese mice fed a high-fat diet

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

29/07/2011

RESUMO

The prevalence of obesity is increasing every year, and a becoming a major public health problem. Obesity is considered an important risk factor for development of insulin resistance, dyslipidemia, diabetes mellitus type 2 and arterial hypertension. These are risk factors that act synergistically in the development of erectile dysfunction. However, so far few studies have investigated the mechanisms involved in erectile dysfunction caused by obesity. Therefore, using a model of obesity induced high-fat diet in mice, the present study searched to characterize erectile dysfunction in these animals. Thus, we used functional experiments in vivo and in vitro, biochemical and morphological test. Specifically, the following experiments were performed in corpus cavernosum of control and high-fat fed mice. 1) concentration response curves in vitro to relaxing agents endothelium-dependent (acetylcholine) and NO donor (sodium nitroprusside), as well as to electrical-field stimulation (EFS) (nitrergic relaxations); 2) Concentration-response curves in vitro to the contractile agents phenylephrine ( alfa -1 adrenergic receptor agonist) and endothelin-1, as well as to EFS (neurogenic contraction; 3) measurement of intracavernous pressure in vivo; 4) determination of cGMP levels; 5) hystomorfometric measurement. Mice treated with high-fat diet showed increased body weight, epididimal fat, total choles-terol and LDL, and insulin resistance. The corpus cavernosum of high-fat fed mice showed impaired intracavernous pressure. The endothelial and nitrergic relaxations were lower in corpus cavernosum of high-fat fed mice. Moreover, the contractile responses induced by phenylephrine, endothelin-1 and electrical stimulation were increase in this animals. The cGMP levels were lower in corpus cavernosum of high-fat fed mice in comparison with control mice. There were no morphological alterations in erectile tissue of mice treated with high-fat diet. To investigate the effect of insulin resistance in erectile function, we treated the animals with insulin sensitizer, metformin, for 14 days (300 mg /kg/day). Metformin treatment restored the impaired endothelium-dependent and nitrergic relaxations, and the enhanced contractile response to phenylephrine in the corpus cavernosum of high-fat fed mice, without affecting the body weight and epididymal fat. In conclusion, our data shows that treatment with high-fat diet for 10 weeks reduces the intracavernous pressure, as well as the endothelial and nitrergic cavernosal relaxations. Concomitantly, this treatment increases the contractile responses, in vitro. Metformin treatment restored the insulin sensitivity and the erectile dysfunction, suggesting that erectile dysfunction in high-fat fed mice is the result of insulin resistance associated with obesity

ASSUNTO(S)

corpo cavernoso Óxido nítrico obesidade resistência à insulina corpus cavernosum nitric oxide obesity insulin resistance

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