Terminal Arteriolar Network Structure/Function and Plasma Cytokine Levels in db/db and ob/ob Mouse Skeletal Muscle

P>Objective: To investigate the terminal arteriolar network structure and function in relation to circulating plasma cytokine levels in db/db, ob/ob, and their genetic background control, C57/bl6, mice. Methods: Arteriolar network size and erythrocyte distribution were observed in the resting cremaster muscle (n = 45, pentobarbital 50 mg/kg i.p.). Structural remodeling and inflammatory state were related to 21 plasma cytokine levels. Results: db/db networks were shorter, had fewer branches, and smaller diameters than C57/bl6 controls. ob/ob networks were longer, with similar branch numbers, however with non-uniform diameters. Shunting of erythrocytes to the specific terminal arteriolar branches of the network (functional rarefaction) was prominent in db/db and ob/ob, with further evidence of shunting between networks seen as no flow to 50% of ob/ob arteriolar networks. Conclusions: Altered levels of plasma cytokines are consistent with structural remodeling seen in db/db, and a pro-inflammatory state for both db/db and ob/ob. Differences in network structure alone predict overall reduced uniform oxygen delivery in db/db or ob/ob. Shunting probably increases heterogeneous oxygen delivery and is strain-dependent.