Adipocyte-derived factor reduces vasodilatory capability in ob-/ob- mice.
Obesity is associated with impaired functional hyperemic response. We have shown that ATP-sensitive potassium (K(ATP)) channels are important in mediating functional vasodilation. Adipocyte-derived factors (ADFs) can alter vascular tone via opening K(ATP) channels. We hypothesize that, in an animal model of obesity, ADFs will decrease basal arteriolar tone by opening K(ATP) channels, resulting in an attenuated functional vasodilation. We used wild-type (WT) mice and ob(-)/ob(-) mice (ob) to test this hypothesis. The spinotrapezius muscle was prepared for the microcirculatory observation of arcade arterioles, and we measured the vasodilatory responses to muscle stimulation. The basal arteriolar diameter was larger in ob mice compared with WT mice. The K(ATP) channel inhibitor glibenclamide (10 microM) decreased arteriolar diameter in ob mice with no effect in WT mice. The increase in arteriolar diameter induced by muscle stimulation was attenuated in ob mice compared with WT mice. To determine the mechanisms for the opening of K(ATP) channels, fat was collected from the ob mice, subcutaneous fat from around the spinotrapezius muscle (OBSF) or visceral fat (OBVF) and was incubated in physiological saline solution (PSS). The vasodilatory responses to the fat-conditioned PSS were determined in WT mice. Treatment with OBSF- or OBVF -conditioned PSS increased the arteriolar diameters in WT mice, a dilation that was inhibited by glibenclamide. The absolute diameters induced by muscle stimulation were not altered by the fat-conditioned PSS. These results suggest that, in ob mice, local ADFs reduce the functional vasodilatory capability via opening K(ATP) channels.
Xiang
Lusha
L
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. Lxiang2@physiology.umsmed.edu
Hester
Robert L
RL
D000241:Adenosine / Q000494:pharmacology; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000502:physiology*; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D054086:KATP Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D000241:Adenosine; D005905:Glyburide