title: Regional heterogeneity of α-adrenoreceptor subtypes in arteriolar networks of mouse skeletal muscle.
abstract: Activation of vascular adrenoreceptors (ARs) governs the magnitude and distribution of muscle blood flow in accord with the distribution of AR subtypes. Functional studies in the rat cremaster muscle indicate that α1ARs predominate in proximal arterioles (first-order, 1A) while α2ARs predominate in distal arterioles (third-order, 3A). However, little is known of AR subtype distribution in arteriolar networks of locomotor skeletal muscles, particularly in the mouse. We tested the hypotheses that functional AR subtypes exhibit heterogeneity among branches of arteriolar networks in a locomotor muscle and that the nature of this heterogeneity can vary between muscles having diverse functions. In anaesthetized male C57BL/6J mice (3 months old), concentration-response curves (10(-9) m to 10(-5) m, 0.5 log increments) were evaluated in the gluteus maximus muscle superfused with physiological saline solution (35°C, pH 7.4; n ≥ 5 per group). Noradrenaline (NA, non-selective αAR agonist) constricted 1A, 2A and 3A with similar potency and efficacy. Phenylephrine (PE; α1AR agonist) evoked greater (P < 0.05) constriction in 3A (inhibited by 10(-8) m prazosin; α1AR antagonist) while UK 14304 (UK; α2AR agonist) evoked greater (P < 0.05) constriction in 1A (inhibited by 10(-7) m rauwolscine; α2AR antagonist). Isoproterenol (isoprenaline; βAR agonist) dilated 1A, 2A and 3A near-maximally with similar potency and efficacy; these dilatations were inhibited by 10(-7) m propranolol (βAR antagonist) which otherwise had no effect on responses to NA, PE, or UK. Complementary experiments in the mouse cremaster muscle revealed a pattern of αAR subtype distribution that, while distinct from the gluteus maximus muscle, was consistent with that reported for the rat cremaster muscle. We conclude that functional αAR subtype distribution in arteriolar networks of skeletal muscle varies with muscle function as well as vessel branch order.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Moore
authors.forename: William F
authors.initials: WF
authors.lastname: Jackson
authors.forename: Steven S
authors.initials: SS
authors.lastname: Segal
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D000068438:Brimonidine Tartrate; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin
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