DIVERGENCE BETWEEN ARTERIAL PERFUSION AND FATIGUE RESISTANCE IN SKELETAL MUSCLE IN THE METABOLIC SYNDROME

Abstract

The obese Zucker rat (OZR) exhibits many vascular alterations, although the integrated impact on active hyperemia remains unclear. Pressor responses and skeletal muscle perfusion were assessed in lean Zucker rats (LZR) and OZR during adrenergic stimulation (phenylephrine), challenge with thromboxane (U46619) and endothelium‐dependent dilation (methacholine). OZR were hypertensive vs. LZR, but this was abolished by adrenoreceptor blockade (phentolamine); pressor responses to U46619 were similar and were abolished by the PGH2/TxA2 receptor antagonist, SQ‐29548. Depressor responses to methacholine were impaired in OZR, but improved by the antioxidant TEMPOL. Active hyperemia to gastrocnemius muscle was restrained by adrenergic constriction in OZR, although this diminished with increased VO2. O2 extraction, reduced in OZR across levels of metabolic demand, was improved by TEMPOL or SQ‐29548; phentolamine did not impact extraction and neither TEMPOL nor SQ‐29548 improved perfusion. While VO2 and muscle performance were reduced in OZR, treatment with all three agents improved outcomes; individual agents were less effective. These data suggest that contributions of vascular dysfunction to perfusion, VO2 and muscle performance are spatially distinct, with adrenergic constriction impacting proximal resistance and endothelial dysfunction impacting distal exchange. (NIH DK64668, RR2865AR)