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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/H689    most recent 01327.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Xiang, L. Articles by Hester, R. L. PubMed PubMed Citation Articles by Xiang, L. Articles by Hester, R. L.

Adipocyte-derived factor reduces vasodilatory capability in ob^–/ob^– mice

Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi

Submitted 23 December 2008 ; accepted in final form 29 May 2009

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 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 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.

obesity; cytokines; vasodilation; adipose tissue; and potassium channels