Angiotensin II Type 1 and Type 2 Receptors Regulate Basal Skeletal Muscle Microvascular Volume and Glucose Use
Angiotensin II Type 1 and Type 2 Receptors Regulate Basal Skeletal Muscle Microvascular Volume and Glucose Use
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血管紧张素 II 1 型和 2 型受体调节基底骨骼肌微血管容量和葡萄糖使用
DOI：
10.1161/hypertensionaha.109.145409
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发表时间：
2010-02-01
期刊：
影响因子：
8.3
通讯作者：
Liu, Zhenqi
中科院分区：
文献类型：
--
作者：
Chai, Weidong;Wang, Wenhui;Liu, Zhenqi
血管紧张素II通过1型受体（AT1R）引起血管收缩，通过2型受体（AT2R）引起血管扩张。两者都在肌肉微血管中表达，在那里发生底物交换。它们是否调节基底肌微血管灌注和底物代谢尚不清楚。我们测量了大鼠在以每分钟1或100 ng/kg的速度全身输注血管紧张素II时的微血管血容量（MBV），微血管表面积和灌注的量度。每一种都导致肌肉MBV显著增加。同样，给予AT1R阻滞剂氯沙坦使肌肉MBV增加3倍（P<0.001）。后腿葡萄糖提取量和肌间质氧饱和度同时增加2 ~ 3倍。相比之下，输注AT2R拮抗剂PD123319可显著降低肌肉MBV≥80% （P<0.001）。这与后腿葡萄糖提取和肌肉氧饱和度的显著降低有关。AT2R的拮抗作用和NO合成酶的抑制作用均阻断氯沙坦诱导的肌肉MBV和葡萄糖摄取的增加。综上所述，血管紧张素II同时作用于AT1R和AT2R，调节基底肌微血管灌注。基础AT1R张力限制肌肉MBV和葡萄糖提取，而基础AT2R活性增加肌肉MBV和葡萄糖摄取。AT1R和AT2R活性平衡的药理学操作提供了改善葡萄糖代谢的潜力。
Angiotensin II causes vasoconstriction via the type 1 receptor (AT1R) and vasodilatation through the type 2 receptor (AT2R). Both are expressed in muscle microvasculature, where substrate exchanges occur. Whether they modulate basal muscle microvascular perfusion and substrate metabolism is not known. We measured microvascular blood volume (MBV), a measure of microvascular surface area and perfusion, in rats during systemic infusion of angiotensin II at either 1 or 100 ng/kg per minute. Each caused a significant increase in muscle MBV. Likewise, administration of the AT1R blocker losartan increased muscle MBV by >3-fold (P<0.001). Hindleg glucose extraction and muscle interstitial oxygen saturation simultaneously increased by 2- to 3-fold. By contrast, infusing AT2R antagonist PD123319 significantly decreased muscle MBV by ≥80% (P<0.001). This was associated with a significant decrease in hindleg glucose extraction and muscle oxygen saturation. AT2R antagonism and inhibition of NO synthase each blocked the losartan-induced increase in muscle MBV and glucose uptake. In conclusion, angiotensin II acts on both AT1R and AT2R to regulate basal muscle microvascular perfusion. Basal AT1R tone restricts muscle MBV and glucose extraction, whereas basal AT2R activity increases muscle MBV and glucose uptake. Pharmacological manipulation of the balance of AT1R and AT2R activity affords the potential to improve glucose metabolism.