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Impaired Vascular K ATP Function Attenuates Exercise Capacity in Obese Zucker Rats
Author(s) -
Lu Silu,
Xiang Lusha,
Clemmer John S.,
Gowdey Andrew R.,
Mittwede Peter N.,
Hester Robert L.
Publication year - 2013
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12065
Subject(s) - cromakalim , apocynin , vasodilation , glibenclamide , superoxide , medicine , vascular smooth muscle , endocrinology , chemistry , contraction (grammar) , biochemistry , smooth muscle , enzyme , diabetes mellitus
Objective Obese subjects exhibit decreased exercise capacity ( V O 2max ). We have shown that vascular K ATP channel mediates arteriolar dilation to muscle contraction. We hypothesize that exercise capacity is decreased in obesity due to impaired vascular K ATP function. Methods The V O 2max was measured in LZR and OZR by treadmill running before and following treatment with the K ATP blocker glibenclamide i.p. One week later, the spinotrapezius muscle was prepared for in vivo microscopy. Arcade arteriolar diameters were measured following muscle contraction or application of the K ATP opener cromakalim before and after glibenclamide application. In additional animals, LZR and OZR were treated with apocynin for five weeks. V O 2max and arteriolar dilation experiments were repeated. Results The OZR exhibited decreased V O 2max , functional and cromakalim‐induced vasodilation as compared with LZR . Glibenclamide had no effect on V O 2max and functional vasodilation in OZR , but significantly inhibited responses in LZR . Vascular superoxide levels and NADPH oxidase activity were increased in OZR , but reduced in apocynin‐treated OZR . Apocynin increased the V O 2max , functional and cromakalim‐induced vasodilation in OZR with no effect in LZR . Conclusions Exercise capacity is dependent on vascular K ATP channel function. The reduced exercise capacity in OZR appears to be due in part to superoxide‐mediated impairment in vascular K ATP function.