Greater α1‐ and α2‐Adrenergic Mediated Vasoconstriction in Contracting Skeletal Muscle of Type 2 Diabetic Humans

Abstract

Type 2 diabetics (T2D) have diminished exercise capacity (VO2max), an independent risk factor for cardiovascular disease. Inadequate blood flow during exercise largely contributes to the reduced VO2max characteristic of T2D. Offsetting sympathetic‐mediated, α‐adrenergic vasoconstriction in contracting skeletal muscle (i.e., functional sympatholysis) is a key regulatory mechanism matching O2 supply (blood flow) with demand (metabolism). Thus, we studied if functional sympatholysis was impaired in 18 T2D (13M/5F) versus 15 control subjects (10M/5F) using intra‐arterial infusions of phenylephrine (PE, α1‐agonist) and dexmedetomidine (DEX, α2‐agonist) at rest, as well as during handgrip exercise. Handgrip exercise trials lasted for 6min at a workload of 20% maximum grip strength. Steady‐state (SS) blood flow was achieved during the first 3min with either PE or DEX infused during the latter 3min. Forearm blood flow (FBF, ml/min) was calculated using brachial artery diameter and blood velocity measured via Doppler ultrasound. Forearm vascular conductance (FVC, ml/min/100mmHg) was calculated using FBF and mean arterial pressure (MAP, measured intra‐arterially). Both FBF and FVC were calculated from data averaged over the final 30sec of rest and SS exercise (before and during infusions). Functional sympatholysis for both PE and DEX trials (resting and exercise) was quantified as: ((SS FVCwith drug – SS FVCpre‐drug)/SS FVCpre‐drug)x100%. T2D and control subjects were of similar age (60±9 vs. 60±9years, p=0.87) and body mass index (30.9±5.5 vs. 29.5±4.6kg/m2, p=0.42); however, VO2max was lower in T2D compared to controls (20.7±5.9 vs. 27.7±8.5ml/kg/min, respectively, p<0.01). No differences in resting FBF, FVC, α1‐ or α2‐mediated vasoconstriction were observed between T2D and controls (p>0.05 for all). In response to handgrip exercise, T2D had 20% lower FBF (166±71 vs. 199±66ml/min, p=0.09) and 24% lower FVC (142±59 vs. 177±52ml/min/100mmHg, p<0.05) compared to controls, respectively. Of particular interest, α1‐ (−16.6±5.9 vs. −10.9±4.3%, p<0.01) and α2‐mediated (−23.8±6.6 vs. 19.5±7.0%, p<0.05) vasoconstriction during handgrip exercise was greater in T2D compared to controls. These data suggest impaired functional sympatholysis may contribute to the diminished exercise capacity of T2D and therefore, could increase their risk of developing cardiovascular disease.Support or Funding InformationAmerican Diabetes Association 1‐16‐ICTS‐015This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.