Activation of the cannabinoid receptor 2 increases renal perfusion.
Activation of the cannabinoid receptor 2 increases renal perfusion.
复制标题
大麻素受体 2 的激活会增加肾灌注。
DOI：
10.1152/physiolgenomics.00001.2019
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发表时间：
2019
影响因子：
4.6
通讯作者：
Park,F
中科院分区：
文献类型：
--
作者：
Pressly,JD;Soni,H;Jiang,S;Wei,J;Liu,R;Moore,BM;Adebiyi,A;Park,F
急性肾损伤(AKI)是一个与慢性肾脏疾病进展相关的日益严重的临床问题。大麻素受体2(CB2)的激活已经被证明可以减轻AKI引起的一些有害的肾小管效应，但它在肾血管系统中的作用还没有完全被描述。在这项研究中，我们研究了我们的新型CB2受体激动剂SMM-295对肾血管系统的影响，方法是用激光多普勒血流仪评估肾皮质的血流灌注和分离的传入小动脉的管腔直径的变化。在本研究中，静脉输注SMM295(6 mg/kg)显著增加了麻醉C57BL/6J小鼠的肾皮质灌注量(13.8 ± 0.6%；P<；0.0001；n=7)，而载体组(0.1±1.5%；n=10)恢复到基线水平。这种作用不依赖于CB1受体的激活(甲基苯乙酰胺，6 mg/kg iv)，在使用SMM-295(6 mg/kg iv)的Cnr2基因敲除小鼠中，这种作用主要被取消。用辣椒素阻断肾传入神经可阻断SMM-295依赖的肾皮质灌注量的增加，肾血流量的增加不依赖于环氧合酶或一氧化氮合酶合成的产物。Cb2受体激活引起的肾脏血流灌注增加也归因于直接的血管效应，因为SMM295(5μM)使去甲肾上腺素预缩窄的传入小动脉的内径显著增加37 ± 7%(P<；0.0001；n=4)。这些数据为SMM-295通过激活血管和非血管CB2受体促进肾血管扩张的潜在益处提供了新的见解，并为治疗影响肾血流动力学的肾损伤提供了新的治疗靶点。
Acute kidney injury (AKI) is an increasing clinical problem that is associated with chronic kidney disease progression. Cannabinoid receptor 2 (CB2) activation has been shown to mitigate some of the deleterious tubular effects due to AKI, but its role on the renal vasculature has not been fully described. In this study, we investigated the effects of our novel CB2 receptor agonist, SMM-295, on renal vasculature by assessing cortical perfusion with laser Doppler flowmetry and changes in luminal diameter with isolated afferent arterioles. In this study, intravenously infused SMM-295 (6 mg/kg) significantly increased cortical renal perfusion (13.8 ± 0.6%;P< 0.0001;n= 7) compared with vehicle (0.1 ± 1.5%;n= 10) normalized to baseline values in anesthetized C57BL/6J mice. This effect was not dependent upon activation of the CB1 receptor (met-anandamide; 6 mg/kg iv) and was predominantly abolished inCnr2knockout mice with SMM-295 (6 mg/kg iv). Ablation of the renal afferent nerves with capsaicin blocked the SMM-295-dependent increase in renal cortical perfusion, and the increased renal blood flow was not dependent upon products synthesized by cyclooxygenase or nitric oxide synthase. The increased renal perfusion by CB2 receptor activation is also attributed to a direct vascular effect, since SMM-295 (5 μM) engendered a significant 37 ± 7% increase (P< 0.0001;n= 4) in luminal diameters of norepinephrine-preconstricted afferent arterioles. These data provide new insight into the potential benefit of SMM-295 by activating vascular and nonvascular CB2 receptors to promote renal vasodilation, and provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.