Article Title

Basal production of nitric oxide (NO) and non-NO vasodilators in the forearm microcirculation in Type 2 diabetes: Associations with blood pressure and HDL cholesterol

Abstract

We examined basal forearm microcirculatory blood flow (FBF) using venous occlusive strain-gauge plethysmography in 47 middle-aged men and women [55 ± 1 years] with Type 2 diabetes and 15 age-matched healthy individuals [52 ± 3 years], all receiving aspirin. Blood flow was also measured following infusion of NG-monomethyl-l-arginine into the brachial artery to inhibit basal NO release (FBF + l-NMMA). Acetylcholine (ACh) and sodium nitroprusside (SNP) were administered to assess endothelium-dependent and endothelium-independent functions. Compared with controls, diabetic subjects had significantly lower vasodilatory responses to ACh and SNP (p < 0.05 for each). Basal FBF and FBF + l-NMMA were increased in diabetic subjects compared with controls (2.4 ± 0.2 ml/100 ml/min versus 1.7 ± 0.2 ml/100 ml/min, p = 0.02 and 1.9 ± 0.1 ml/100 ml/min versus 1.2 + 0.1 ml/100 ml/min, p = 0.01, respectively) whereas the change in FBF following l-NMMA was greater in the controls (−27% versus −19%, p = 0.05). Amongst the diabetic subjects, pulse pressure and HDL cholesterol were independent predictors of FBF (b = 0.04 ± 0.01, adjusted r2 = 0.21 and p = 0.001, and b = 3.3 ± 1.2, adjusted r2 = 0.12 and p = 0.007, respectively) and FBF + l-NMMA (b = 0.03 ± 0.01, adjusted r2 = 0.20, p = 0.002 and b = 2.1 ± 0.9, adjusted r2 = 0.09 and p = 0.02, respectively). Diastolic blood pressure predicted the change in FBF with l-NMMA (b = −1.02 ± 0.32, adjusted r2 = 0.20 and p = 0.003). Our findings suggest that well controlled T2DM patients have impaired agonist-mediated vasodilatation of the forearm resistance arteries that is associated with impaired basal release of nitric oxide but an increase in the release of non-NO vasodilators. The latter may be a compensatory response to increased arterial stiffness and may be facilitated by an effect of HDL.

Keywords

peer-reviewed

 

Link to Publisher Version (DOI)

http://doi.org/10.1016/j.diabres.2005.05.008