Premium
Vascular ATP‐sensitive K + (K ATP ) Channels: Sex and Fiber‐type Differences in the Support of Contracting Muscle Blood Flow and Interstitial PO 2
Author(s) -
Colburn Trenton D.,
Weber Ramona E.,
Schulze Kiana M.,
Hageman K. Sue,
Behnke Bradley J.,
Musch Timothy I.,
Poole David C.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05987
Subject(s) - medicine , glibenclamide , endocrinology , chemistry , blood flow , oxidative phosphorylation , diabetes mellitus , biochemistry
Glibenclamide (GLI), prescribed to Type II diabetes patients, enhances insulin release by inhibiting pancreatic K ATP channels. K ATP channels support maximal aerobic capacity (V̇O 2 max; determined by cardiac output (Q̇) and O 2 utilization within contracting skeletal muscle (arterial‐venous O 2 difference)) and blood flow during treadmill running in male rats. High‐intensity exercise tolerance (critical speed, CS) is impaired by GLI but is not correlated with reductions in resting cardiac function (Q̇) which highlights the role for peripheral vascular K ATP channel function to protect against fatigue. Whether muscle O 2 delivery‐utilization matching (interstitial PO 2 , PO 2 is ) is impaired by GLI in a fiber‐type specific manner, and whether sex differences exist in K ATP function, are unknown. PURPOSE We hypothesized that local inhibition of K ATP channels via GLI would decrease PO 2 is and blood flow within contracting fast‐twitch oxidative (mixed gastrocnemius (MG)) and slow‐twitch oxidative (soleus (SOL)) muscles with females (F) exhibiting the greatest reduction. METHODS Male (n=8), female (n=9, proestrus) and ovariectomized female (F+OVX; n=11) Sprague‐Dawley rats were utilized in these experiments. PO 2 is was determined, before and after GLI superfusion (5 mg kg −1 ), via phosphorescence quenching (G4) in the exposed MG and SOL muscles during electrically‐induced twitch contractions (180 s, 7V, 1Hz). Blood flow was assessed via infusion of fluorescent‐labeled microspheres (15 μm) at 180 s of contractions. RESULTS GLI reduced MG blood flow (female: 49 ± 9 vs 34 ± 5; male: 50 ± 5 vs 35 ± 4 ml min −1 100 g −1 ), nadir PO 2 is (female: 5.9 ± 0.3 vs 4.7 ± 0.3; male: 6.8 ± 0.7 vs 5.5 ± 0.4) and end‐contraction PO 2 is (female: 7.3 ± 0.5 vs 6.1 ± 0.5; male: 8.9 ± 1.1 vs 7.2 ± 0.5 mmHg), but did not impact SOL, of female and male rats (p<0.05). Conversely, in F+OVX, PO 2 is was reduced in the SOL (nadir: 12.5 ± 1.5 vs 8.8 ± 0.9; end‐contraction: 14.5 ± 1.5 vs 10.2 ± 1.1 mmHg; p<0.05), but not MG. CONCLUSION These data support the role of vascular K ATP channels in supporting muscle O 2 delivery and high‐intensity exercise tolerance by matching O 2 delivery‐utilization with ovariectomy shifting K ATP channel effects from fast‐ to slow‐twitch muscles. Thus GLI treatment in diabetic and other cardiovascular disease patients may potentiate exercise intolerance, especially for post‐menopausal females where compromised slow‐twitch fiber function impairs the ability or willingness to engage in low intensity exercise. Support or Funding Information Supported by NIH Grants: HL108328 (D.C.P and T.I.M) and F31HL145981 (T.D.C)