α‐ADRENOCEPTOR‐MEDIATED VASOCONSTRICTION IS NOT INVOLVED IN IMPAIRED FUNCTIONAL VASODILATION IN THE OBESE ZUCKER RAT

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Abstract
1 Obesity/metabolic syndrome is associated with augmented a‐adrenoceptor sensitivity and impaired hyperaemic responses to exercise. Thus, it is possible that this elevated a‐adrenoceptor constriction contributes to the blunted hyperaemic response. 2 Male lean and obese Zucker rats were instrumented for acute measurements of blood pressure (BP) and iliac blood flow (BF). Changes in BP and BF were determined in anaesthetized animals in response to intravenous administration of increasing doses of the a1‐adrenoceptor agonist phenylephrine (PE). Once BF and BP returned to normal, a single bolus of the a‐adrenoceptor antagonist phentolamine (0.5 mg) was administered. In separate animals, the spinotrapezius muscle was exteriorized for direct in situ observation of the microcirculation in response to phentolamine and muscle contraction. 3 Administration of PE demonstrated that iliac BF is highly autoregulated in the face of increasing perfusion pressure. Iliac conductance following phentolamine was significantly greater in obese rats. Following phentolamine administration, iliac vascular conductance was significantly greater in obese rats compared with lean animals. However, a‐adrenoceptor blockade did not significantly alter arteriolar diameter in the spinotrapezius muscle during muscle contraction in either lean or obese animals. 4 These results suggest a greater contribution of the a‐adrenoceptors in basal hindlimb vascular tone in obese rats. Furthermore, an augmented a‐adrenoceptor‐mediated vasoconstriction may not contribute to the impaired functional dilation in anaesthetized obese rats.