Faculty Collaboration Database

Greater α₁-adrenergic-mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes. Am J Physiol Heart Circ Physiol 2020 Oct 01;319(4):H797-H807

Date

08/22/2020

Pubmed ID

32822215

DOI

10.1152/ajpheart.00532.2020

Scopus ID

2-s2.0-85091470238 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

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: [(FVC_{with drug} - FVC_predrug)/FVC_predrug × 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.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 α₁-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.

Author List

Bock JM, Hughes WE, Ueda K, Feider AJ, Hanada S, Kruse NT, Iwamoto E, Casey DP

Author

William E. Hughes Postdoctoral Fellow in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-1 Receptor Agonists
Aged
Diabetes Mellitus, Type 2
Exercise Tolerance
Female
Forearm
Humans
Hyperemia
Infusions, Intra-Arterial
Male
Middle Aged
Muscle Contraction
Muscle, Skeletal
Phenylephrine
Random Allocation
Vasoconstriction