Heightened norepinephrine-mediated vasoconstriction in type 2 diabetes

Adrenergic responsiveness (AR) appears to be increased in subjects with dia betes, but measurement of arterial AR in normotensive people with type 2 di abetes mellitus has not been previously reported. We sought to determine wh ether, compared with control subjects, there is increased arterial AR in ty pe 2 diabetes mellitus and its relationship to the level of systemic sympat hetic nervous system activity (SNSa). We studied 15 type 2 diabetic subject s aged 57 +/- 3 years without hypertension or clinical signs of autonomic n europathy and 13 age-matched control subjects aged 55 +/- 3 years. We asses sed vascular alpha-AR by measuring forearm blood flow (FABF) by venous occl usion plethysmography during intrabrachial artery norepinephrine (NE) and p hentolamine infusions, as well as arterial plasma NE levels and the extrava scular NE release rate (NE2) derived from H-3-NE kinetics, as estimates of systemic SNSa. The vasoconstricting effect of NE during intrabrachial arter y NE infusion was greater in type 2 diabetes compared with control subjects (P =.02). The vasodilating effect of phentolamine was greater in type 2 di abetics compared with control subjects (P=.05), suggesting increased endoge nous arterial or-adrenergic tone. Arterial plasma NE revels (control v;type 2, 1.8 +/- 0.10 v 1.84 +/- 0.14 nmol/L, P = .86) and NE2 (control v type 2 , 11.8 +/- 1.54 v 13.3 +/- 0.89 nmol/min/m(2), P =.39) were similar in the two groups, In summary, in type 2 diabetes compared with control subjects, (1) the vasoconstriction response to intraarterial NE is greater, (2) plasm a NE and NE2 are similar, suggesting similar levels of systemic SNSa, and ( 3) arterial alpha-adrenergic tone is greater. We conclude that subjects wit h type 2 diabetes demonstrate inappropriately increased alpha-AR for their level of systemic SNSa, Copyright (C) 1999 by W.B. Saunders Company.