Submitted on December 23, 2008
Revised on May 29, 2009
Accepted on May 29, 2009
Adipocyte derived factor reduces vasodilatory capability in ob-/ob- mice
Lusha Xiang1* and Robert L. Hester2
1 UMC
2 University of Mississippi Medical Center
* To whom correspondence should be addressed. E-mail: lxiang2{at}physiology.umsmed.edu.
Obesity is associated with impaired functional hyperemic response. We have shown that KATP channels are important in mediating functional vasodilation. Adipocyte derived factors (ADFs) can alter vascular tone via opening KATP channels. We hypothesize that, in an animal model of obesity, ADFs will decrease basal arteriolar tone by opening KATP channels, resulting in an attenuated functional vasodilation. We used wild type mice (WT) 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 as compared with WT mice. The KATP channel inhibitor glibenclamide (10 µM) 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 as compared with WT mice. To determine the mechanisms for the opening of KATP channels, fat was collected from the ob mice, subcutaneous fat from around the spinotrapezius muscle (OBSF) or visceral fat (OBVF) and was incubated in 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 which 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 KATP channels.
