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

机译:小鼠骨骼肌小动脉网络中α-肾上腺素受体亚型的区域异质性

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摘要

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 (10−9m to 10−5m, 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 10−8m prazosin; α1AR antagonist) while UK 14304 (UK; α2AR agonist) evoked greater (P < 0.05) constriction in 1A (inhibited by 10−7m rauwolscine; α2AR antagonist). Isoproterenol (isoprenaline; βAR agonist) dilated 1A, 2A and 3A near-maximally with similar potency and efficacy; these dilatations were inhibited by 10−7m 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.
机译:血管肾上腺素能受体(ARs)的激活控制肌肉血流的大小和分布,与AR亚型的分布相一致。大鼠提睾肌的功能研究表明,α1ARs在近端小动脉中占主导(一阶,1A),而α2ARs在远端小动脉中占主导(三阶,3A)。然而,关于运动型骨骼肌的小动脉网络中AR亚型分布的了解很少,特别是在小鼠中。我们测试了以下假设:功能性AR亚型在运动性肌肉的小动脉网络分支之间表现出异质性,并且这种异质性的性质在具有多种功能的肌肉之间会有所不同。在麻醉的雄性C57BL / 6J小鼠(3个月大)中,评估了浓度-反应曲线(10 -9 m至10 -5 m,0.5 log增量)。臀大肌肌肉注入生理盐水溶液(35°C,pH 7.4;每组n≥5)。去甲肾上腺素(NA,非选择性αAR激动剂)可收缩1A,2A和3A,效力和功效相似。苯肾上腺素(PE;α1AR激动剂)在3A中引起更大的收缩(P <0.05)(被10 -8 m哌唑嗪抑制;α1AR拮抗剂),而UK 14304(UK;α2AR激动剂)引起的收缩更大(P <0.05) 0.05)1A收缩(被10 −7 m狼疮素;α2AR拮抗剂抑制)。异丙肾上腺素(异丙肾上腺素;βAR激动剂)以相似的效价和功效最大程度地扩张了1A,2A和3A。这些扩张被10 −7 m普萘洛尔(βAR拮抗剂)抑制,否则对NA,PE或UK的反应没有影响。在小鼠的提睾肌中进行的补充实验揭示了αAR亚型分布的模式,该模式与臀大肌不同,但与大鼠的提睾肌一致。我们得出结论,骨骼肌小动脉网络中功能性αAR亚型分布随肌肉功能以及血管分支顺序而变化。

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