HYPERREACTIVITY TO NITROVASODILATORS IN FOREARM VASCULATURE IS RELATED TO AUTONOMIC DYSFUNCTION IN INSULIN-DEPENDENT DIABETES-MELLITUS

Background The link between diabetes and vascular disease is poorly un derstood. Data regarding endothelial function in vivo in patients with insulin-dependent diabetes mellitus (IDDM) have been inconsistent wit h in vitro studies demonstrating hyperglycemia-induced impairments in endothelium-dependent vasodilation. Methods and Results We determined whether alterations in neural control of the vascular tone might contr ibute to blood flow responses to intrabrachial infusions of acetylchol ine (ACh), sodium nitroprusside (SNP), and L-N-monomethyl-arginine (L- NMMA) in 22 men with IDDM (12 with normoalbuminuria, HbA(1c)=8.6+/-0.3 %; 10 with macroalbuminuria, HbA(1c)=8.6+/- 0.3%) and 11 matched norma l men. Autonomic function was assessed from reflex vasoconstriction to cold, the blood pressure response to standing and hand grip, and hear t rate variation, including spectral analysis, during controlled breat hing, and the Valsalva maneuver. IDDM with macroalbuminuria exhibited hyperresponsiveness to both ACh and SNP compared with the patients wit h normoalbuminuria or normal subjects. Reflex sym pathetic vasoconstri ction to cold was severely impaired in the IDDM patients with macroalb uminuria (-19+/-6%) compared with normoalbuminuric patients (-39+/-58, P<.05) and normal subjects (-54+/-7%, P<.001). The macroalbuminuric p atients also had evidence of autonomic dysfunction during controlled a nd deep breathing tests and during the Valsalva maneuver. Within the g roup of IDDM patients, neither the urinary albumin excretion rate nor other parameters such as HbA(1c) or serum cholesterol correlated with forearm blood flow during the vasoactive drug infusions. There were, h owever, significant inverse correlations between several measures of b oth sympathetic and parasympathetic autonomic functions and vascular h yperresponsiveness to SNP and ACh. For example, the Valsalva ratio was inversely correlated with the increase in blood flow in response to i nfusion of 3 (r=-.74, P<.001) and 10 (r=-.73, P<.001) mu g/min SNP and 7.5 (r=-.73, P<.001) and 15 (r=-.75, P<.001) mu g/min ACh. Conclusion s These data are consistent with idea that altered neurotransmission i s an important determinant of vascular reactivity of diabetic blood ve ssels to nitrovasodilators in vivo.