Altered post-capillary and collecting venular reactivity in skeletal muscle with metabolic syndrome

While research into vascular outcomes of the metabolic syndrome has focused on arterial/arteriolar and capillary levels, investigation into venular function and how this impacts responses has received little attention. Using the in situ cremaster muscle of obese Zucker rats (OZR; with lean Zucker rats (LZR) as controls), we determined indices of venular function. At approximate to 17weeks of age, skeletal muscle post-capillary venular density was reduced by approximate to 20% in LZR vs. OZR, although there was no evidence of remodelling of the venular wall. Venular tone at approximate to 25m (post-capillary) and approximate to 75m (collecting) diameter was elevated in OZR vs. LZR. Venular dilatation to acetylcholine was blunted in OZR vs. LZR due to increased oxidant stress-based loss of nitric oxide bioavailability (post-capillary) and increased (1)- (and (2)-) mediated constrictor tone (collecting). Venular constrictor responses in OZR were comparable to LZR for most stimuli, although constriction to (1)-adrenoreceptor stimulation was elevated. In response to field stimulation of the cremaster muscle (0.5, 1, 3Hz), venular dilator and hyperaemic responses to lower frequencies were blunted in OZR, but responses at 3Hz were similar between strains. Venous production of TxA(2) was higher in OZR than LZR and significantly higher than PGI(2) production in either following arachidonic acid challenge. These results suggest that multi-faceted alterations to skeletal muscle venular function in OZR may contribute to alterations in upstream capillary pressure profiles and the transcapillary exchange of solutes and water under conditions of metabolic syndrome.