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-ADRENERGIC CONSTRICTION IMPAIRS DILATOR RESPONSES AND SKELETAL MUSCLE PERFUSION IN OBESE ZUCKER RATS
1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: jfrisbee{at}mcw.edu.
The present study tested the hypothesis that enhanced vascular 
-adrenergic constriction in obese Zucker rats (OZR) impairs arteriolar dilation and perfusion of skeletal muscle at rest and with increased metabolic demand. In lean Zucker rats (LZR) and OZR, isolated gracilis arterioles were viewed via television microscopy, and the contralateral cremaster muscle or gastrocnemius muscle was prepared for study in situ. Gracilis and cremasteric arterioles were challenged with dilator stimuli under control conditions and following blockade of -adrenoreceptors with prazosin (PRZ), phentolamine (PHT) or yohimbine (YOH). Gastrocnemius muscles performed isometric twitch contractions of increasing frequency and perfusion was continuously monitored. In OZR, dilator responses of arterioles to hypoxia (gracilis), wall shear rate (cremaster), acetylcholine and iloprost (both) were impaired vs. LZR. Treatment with PRZ, PHT (and in cremasteric arterioles only, YOH) improved arteriolar reactivity to these stimuli in OZR, although responses remained impaired vs. LZR. Gastrocnemius muscle blood flow was reduced at rest in OZR; this was corrected with i.v. infusion of PHT or PRZ. At all contraction frequencies, blood flow was reduced in OZR vs. LZR; this was improved by infusion of PHT or PRZ at low-moderate metabolic demand only (1 and 3 Hz). At 5Hz, adrenoreceptor blockade did not alter blood flow in OZR from levels in untreated rats. These results suggest that enhanced -adrenergic constriction of arterioles of OZR contributes to impaired dilator responses and reduced muscle blood flow at rest and with mild-moderate (although not with large) elevations in metabolic demand.
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