Greater α1-adrenergic-mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective alpha-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM (n = 30) as well as nondiabetic controls (n = 15) with similar age (59 +/- 9 vs. 60 +/- 9 yr, P = 0.69) and body mass index (31.4 +/- 5.2 vs. 29.5 +/- 4.6 kg/m(2), P = 0.48). Intra-arterial infusion of phenylephrine (alpha(1)-agonist) and dexmedetomidine (alpha(2)-agonist) were used to induce vasoconstriction: [(FVCwith drug = FVCpredrug)/FVCpredrug x 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per alpha-agonist. Patients with T2DM had smaller increases (Delta from rest) in FBF (147 +/- 71 vs. 199 +/- 63 ml/min) and FVC (126 +/- 58 vs. 176 +/- 50 ml center dot min(-1)center dot 100 mmHg(-1), P < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater alpha(1)- (-16.9 +/- 5.9 vs. -11.3 +/- 3.8%) and alpha(2)-mediated vasoconstriction (-23.5 +/- 7.1 vs. -19.0 +/- 6.5%, P < 0.05 for both) versus controls. The magnitude of sympatholysis (Delta in %vasoconstriction between exercise and rest) for PE was lower (worse) in patients with T2DM versus controls (14.9 +/- 12.2 vs. 23.1 +/- 8.1%, P < 0.05) whereas groups were similar during DEX trials (24.6 +/- 12.3 vs. 27.6 +/- 13.4%, P = 0.47). Our data suggest patients with T2DM have attenuated hyperemic and vasodilatory responses to exercise, which could be attributable to greater alpha(1)-mediated vasoconstriction in contracting skeletal muscle. NEW & NOTEWORTHY Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater alpha(1)-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.