Aim: 

Endothelial dysfunction is a key factor in the pathogenesis of myocardial isquemia in type 2 diabetic patients and insulin resistance states. Besides its anabolic actions, insulin has vasoactive effects mediated by the vascular endothelium and the production of nitric oxide (NO) and endothelin-1 (ET-1). The aim of the present study was to assess the vascular effects and intracellular signalling pathways of insulin in coronary arteries from a prediabetic animal model.

Methods: 

Coronary arteries from obese Zucker rat (OZR) and from lean Zucker rats (LZR) were mounted in parallel in vascular myographs. Concentration-response curves for insulin were performed in arteries precontracted with serotonin and the effect of antagonists of the NO and ET-1 pathways were evaluated.

Results: 

OZR exhibited obesity, mild hyperglycemia, hyperinsulinemia and dyslipemia. Insulin induced a vasodilatation slightly lower in OZR than LZR (maximal responses were 345%, n=18, and 475%, n=19, respectively, this effect being blocked by endothelium removal (145% in LZR, p<0.01 vs control, n=8; and 103% in OZR, p<0.01 vs control, n=7) and by blockade of the NO synthase in both LZR y OZR (77%, p<0.01 vs control, n=8; and 108%, p<0.05 vs control, n=8, respectively). Bosentan, an antagonist of ET-1 receptors, did not alter relaxations to insulin in LZR but enhanced those of OZR.

Conclusions: 

Insulin induces an endothelium and NO-mediated vasodilatation in coronary arteries from both LZR and OZR. In the latter, ET-1 production is compensated by an enhanced production of NO thus preserving insulin vasodilator effect.

Supported by grant SAF2006-09191