title: Enhanced arteriolar alpha-adrenergic constriction impairs dilator responses and skeletal muscle perfusion in obese Zucker rats.
abstract: The present study tested the hypothesis that enhanced vascular alpha-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 after blockade of alpha-adrenoreceptors with prazosin, phentolamine, or yohimbine. 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 prazosin and phentolamine (and in cremasteric arterioles only, yohimbine) 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 intravenous infusion of phentolamine or prazosin. At all contraction frequencies, blood flow was reduced in OZR vs. LZR; this was improved by infusion of phentolamine or prazosin at low-moderate metabolic demand only (1 and 3 Hz). At 5 Hz, adrenoreceptor blockade did not alter blood flow in OZR from levels in untreated rats. These results suggest that enhanced alpha-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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. jfrisbee@mcw.edu
authors.forename: Jefferson C
authors.initials: JC
authors.lastname: Frisbee
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000098:blood supply*; D009765:Obesity / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D003000:Clonidine; D011224:Prazosin