Impaired fasting blood glucose is associated with increased endothelin-1 vasoconstrictor tone

Aim/hypothesis: The experimental aim of this study was to determine whether ET-1-mediated vasoconstrictor tone is elevated in adult humans with impaired fasting blood glucose concentrations, independent of other cardiovascular risk factors. Methods: Forearm blood flow (FBF: plethysmography) responses to intra-arterial infusion of selective ET_A receptor blockade (BQ-123: 100nmol/min for 60min) and non-selective ET_A/B blockade (BQ-123+BQ-788: 50nmol/min for 60min) were determined in 28 middle-aged, sedentary adults (17 M/11 F): 14 with normal fasting blood glucose (age: 57±2yr; 6 F/8 M; BMI: 29.2±0.9kg/m²; glucose: 4.9±0.1mmol/L) and 14 impaired fasting blood glucose (58±1yr; 5 F/9 M; 29.6±1.1kg/m²; 5.8±0.1mmol/L) concentrations. Results: Selective ET_A receptor blockade elicited a significantly greater (~20%) increase in FBF in the impaired fasting glucose adults compared with the normoglycemia controls. ET_A/B blockade resulted in a further 2-fold increase (P<0.05) in FBF above that elicited by ET_A receptor antagonism in the impaired fasting glucose but not normal fasting glucose adults. There was a positive correlation between fasting blood glucose levels and the peak vascular responses to ET_A (r=0.44; P<0.05) and ET_A/B (r=0.62; P<0.05) blockade. No other anthropometric, hemodynamic or metabolic variable was correlated with the blood flow responses to ET-1 receptor blockade. Conclusions/interpretation: ET-1-mediated vasoconstrictor tone is elevated in adults with impaired fasting blood glucose concentrations, independent of other cardiometabolic risk factors. Enhanced ET-1 system activity may underlie endothelial vasomotor dysfunction and increased cardiovascular risk in adults with impaired fasting blood glucose concentrations.