Regional heterogeneity of α-adrenoreceptor subtypes in arteriolar networks of mouse skeletal muscle

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 alpha(1)ARs predominate in proximal arterioles (first-order, 1A) while alpha(2)ARs 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 degrees C, pH 7.4; n >= 5 per group). Noradrenaline (NA, non-selective alpha AR agonist) constricted 1A, 2A and 3A with similar potency and efficacy. Phenylephrine (PE; alpha(1)AR agonist) evoked greater (P < 0.05) constriction in 3A (inhibited by 10(-8) m prazosin; alpha(1)AR antagonist) while UK 14304 (UK; alpha(2)AR agonist) evoked greater (P < 0.05) constriction in 1A (inhibited by 10(-7) M rauwolscine; alpha(2)AR antagonist). Isoproterenol (isoprenaline; beta AR agonist) dilated 1A, 2A and 3A near-maximally with similar potency and efficacy; these dilatations were inhibited by 10(-7) M propranolol (beta AR antagonist) which otherwise had no effect on responses to NA, PE, or UK. Complementary experiments in the mouse cremaster muscle revealed a pattern of alpha AR subtype distribution that, while distinct from the gluteus maximus muscle, was consistent with that reported for the rat cremaster muscle. We conclude that functional alpha AR subtype distribution in arteriolar networks of skeletal muscle varies with muscle function as well as vessel branch order.