TY - JOUR
T1 - Basal production of nitric oxide (NO) and non-NO vasodilators in the forearm microcirculation in Type 2 diabetes: Associations with blood pressure nad HDL cholesterol
AU - Woodman, R.J.
AU - Playford, D.A.
AU - Watts, Gerald
PY - 2006
Y1 - 2006
N2 - We examined basal forearm microcirculatory blood flow (FBF) using venous occlusive strain-gauge plethysmography in 47 middle-aged men and women [55 I 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/l 00 ml/min versus 1.7 +/- 0.2 ml/l 00 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 r(2) = 0.21 and p = 0.001, and b = 3.3 +/- 1.2, adjusted r(2) = 0.12 and p = 0.007, respectively) and FBF + L-NMMA (b = 0.03 +/- 0.01, adjusted r(2) = 0.20, p = 0.002 and b = 2.1 +/- 0.9, adjusted r(2) = 0.09 and p = 0.02, respectively). Diastolic blood pressure predicted the change in FBF with L-NMMA (b = -1.02 +/- 0.32, adjusted r(2) 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
AB - We examined basal forearm microcirculatory blood flow (FBF) using venous occlusive strain-gauge plethysmography in 47 middle-aged men and women [55 I 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/l 00 ml/min versus 1.7 +/- 0.2 ml/l 00 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 r(2) = 0.21 and p = 0.001, and b = 3.3 +/- 1.2, adjusted r(2) = 0.12 and p = 0.007, respectively) and FBF + L-NMMA (b = 0.03 +/- 0.01, adjusted r(2) = 0.20, p = 0.002 and b = 2.1 +/- 0.9, adjusted r(2) = 0.09 and p = 0.02, respectively). Diastolic blood pressure predicted the change in FBF with L-NMMA (b = -1.02 +/- 0.32, adjusted r(2) 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
U2 - 10.1016/j.diabres.2005.05.008
DO - 10.1016/j.diabres.2005.05.008
M3 - Article
C2 - 16029909
SN - 0168-8227
VL - 71
SP - 59
EP - 67
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
IS - 1
ER -