当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Insulin resistance in penile arteries from a rat model of metabolic syndrome.

Insulin resistance in penile arteries from a rat model of metabolic syndrome.

Abstract：

BACKGROUND AND PURPOSE:Metabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vascular effects of insulin in penile arteries and whether these effects are impaired in a rat model of insulin resistance and metabolic syndrome. EXPERIMENTAL APPROACH:Penile arteries from obese Zucker rats (OZR) and their counterpart, lean Zucker rats (LZR), were mounted on microvascular myographs and the effects of insulin were assessed in the absence and presence of endothelium and of specific inhibitors of nitric oxide (NO) synthesis, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). Insulin-induced changes in intracellular Ca(2+) concentration [Ca(2+)](i) were also examined. KEY RESULTS OZR exhibited mild hyperglycaemia, hypercholesterolemia, hypertryglyceridemia and hyperinsulinemia. Insulin induced endothelium- and NO-dependent relaxations in LZR that were impaired in OZR. Inhibition of PI3K reduced relaxation induced by insulin and by the beta-adrenoceptor agonist isoprenaline, mainly in arteries from LZR. Antagonism of endothelin 1 (ET-1) receptors did not alter insulin-induced relaxation in either LZR or OZR, but MAPK blockade increased the responses in OZR. Insulin decreased [Ca(2+)](i), a response impaired in OZR. CONCLUSIONS AND IMPLICATIONS:Insulin-induced relaxation was impaired in penile arteries of OZR due to altered NO release through the PI3K pathway and unmasking of a MAPK-mediated vasoconstriction. This vascular insulin resistance is likely to contribute to the endothelial dysfunction and erectile dysfunction associated with insulin resistant states.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Contreras C,Sánchez A,Martínez P,Raposo R,Climent B,García-Sacristán A,Benedito S,Prieto D

doi

10.1111/j.1476-5381.2010.00825.x

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

350-64

issue

eissn

0007-1188

issn

1476-5381

pii

BPH825

journal_volume

161

pub_type

杂志文章

在线工具

Insulin resistance in penile arteries from a rat model of metabolic syndrome.