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.

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 N(G)-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/100ml/min versus 1.7+/-0.2 ml/100ml/min, p=0.02 and 1.9+/-0.1 ml/100ml/min versus 1.2+0.1 ml/100ml/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.