K(ATP)-mediated vasodilation is impaired in obese Zucker rats.
OBJECTIVE
Skeletal muscle blood flow during exercise is impaired in obesity. We tested the hypothesis that the attenuated vasodilation in skeletal muscle arterioles of obese Zucker rats (OZR) is due to altered K(ATP) channel-mediated vasodilation.


METHODS
K(ATP) channel function was determined in isolated skeletal muscle arterioles in response to the K(ATP) opener cromakalim (0.1-10 microM) during normal myogenic tone and alpha-adrenergic-mediated tone (0.1 microM phenylephrine). The spinotrapezius muscle was prepared and the vasodilatory responses to muscle stimulation or iloprost (0.028-2.8 microM) were observed before and after the application of the K(ATP) inhibitor, glibenclamide (10 microM). Channel subunit expression was determined by using western blot analyses.


RESULTS
Cromakalim concentration-response curves were shifted in OZR as compared to lean controls. OZR exhibited impaired functional and iloprost-induced vasodilation as compared to the lean controls. Glibenclamide inhibited the functional and iloprost-induced dilation in the lean rats with no effects in the obese a nimals. Channel subunit expression was similar in femoral arteries.


CONCLUSIONS
The impaired functional vasodilation in the OZR is associated with altered K(ATP) channel sensitivity.
Hodnett
Benjamin L
BL
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Xiang
Lusha
L
Dearman
Jennifer A
JA
Carter
Cory B
CB
Hester
Robert L
RL
D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000096:biosynthesis*; D051381:Rats; D011924:Rats, Zucker; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D010656:Phenylephrine; D016285:Iloprost; D005905:Glyburide