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

• Published in: American journal of physiology. Heart and circulatory physiology 2020-10, Vol.319 (4), p.H797-H807
• Main Authors: Bock, Joshua M, Hughes, William E, Ueda, Kenichi, Feider, Andrew J, Hanada, Satoshi, Kruse, Nicholas T, Iwamoto, Erika, Casey, Darren P
• Format: Article
• Language: English
• Subjects: Agonists; Blood flow; Body mass; Body mass index; Body size; Clinical trials; Conductance; Contraction; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Forearm; Hyperemia; Muscles; Musculoskeletal system; Phenylephrine; Skeletal muscle; Vasoconstriction
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00532.2020

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 α-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/m2, P = 0.48). Intra-arterial infusion of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were used to induce vasoconstriction: [(FVCwith drug − FVCpredrug)/FVCpredrug × 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per α-agonist. Patients with T2DM had smaller increases (Δ from rest) in FBF (147 ± 71 vs. 199 ± 63 ml/min) and FVC (126 ± 58 vs. 176 ± 50 ml·min−1·100 mmHg−1, P < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater α1- (−16.9 ± 5.9 vs. −11.3 ± 3.8%) and α2-mediated vasoconstriction (−23.5 ± 7.1 vs. −19.0 ± 6.5%, P < 0.05 for both) versus controls. The magnitude of sympatholysis (Δ 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 α1-mediated vasoconstriction in contracting skeletal muscle.