Anandamide decreases glomerular filtration rate through predominant vasodilation of efferent arterioles in rat kidneys
Anandamide decreases glomerular filtration rate through predominant vasodilation of efferent arterioles in rat kidneys
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DOI：
10.1097/01.asn.0000130561.82631.bc
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发表时间：
2004-06-01
影响因子：
13.6
通讯作者：
Saruta, T
中科院分区：
文献类型：
--
作者：
Koura, Y;Ichihara, A;Saruta, T
为了确定大麻素（ANA）对肾血流动力学和微循环的影响，在接受15、150和1500 pmol/kg剂量的ANA注射的Sprague-Dawley大鼠中进行清除研究。在高达150 pmol/g的剂量下，ANA显著降低GFR并增加肾血流量（RBF），而不影响平均动脉压（MAP）。在大麻素1型（CB 1）受体拮抗剂AM 251的存在下，只有15 pmol/kg剂量显著增加GFR和RBF而不改变MAP，更高剂量对GFR、RBF或MAP没有影响。相比之下，AM 281，它拮抗大麻素受体非选择性，抑制GFR，RBF和MAP的ANA反应。采用离体血灌流法测定小动脉对ANA的反应。较高剂量的ANA显著增加了传入和传出小动脉的直径，而较低剂量引起主要的传出小动脉扩张。AM 251减弱ANA对传入小动脉的反应，抑制ANA对传出小动脉的反应，而AM 281则抑制两条小动脉的反应。CB 1受体mRNA在传入小动脉中表达，免疫组织化学染色表明传入和传出小动脉中均存在CB 1受体。这些结果表明，ANA通过CB 1和非CB 1受体引起传入小动脉扩张，并通过CB 1受体引起更大的传出小动脉扩张，导致GFR降低和RBF增加，而不影响MAP。
For determining the effects of anandamide (ANA) on renal hemodynamics and microcirculation, a clearance study was performed in Sprague-Dawley rats that received injections of ANA in doses of 15, 150, and 1500 pmol/kg. At doses up to 150 pmol/g, ANA significantly decreased GFR and increased renal blood flow (RBF) without affecting mean arterial pressure (MAP). In the presence of the cannabinoid type 1 (CB 1) receptor antagonist AM251, only the 15- pmol/kg dose significantly increased GFR and RBF without altering MAP, with higher doses having no effect on GFR, RBF, or MAP. By contrast, AM281, which antagonizes cannabinoid receptors nonselectively, inhibited the GFR, RBF, and MAP responses to ANA. The arteriolar responses to ANA were also assessed in vitro by the blood-perfused juxtamedullary nephron technique. Higher doses of ANA significantly increased the diameter of both afferent and efferent arterioles, whereas lower doses elicited predominant efferent arteriolar dilation. AM251 attenuated the afferent arteriolar response to ANA and inhibited the efferent arteriolar response to ANA, whereas AM281 inhibited the responses in both arterioles. The CB1 receptor mRNA was expressed in afferent arterioles, and immunohistochemical staining demonstrated the presence of CB1 receptors in both afferent and efferent arterioles. These results suggest that ANA causes afferent arteriolar dilation via both CB1 and non-CB1 receptors and greater efferent arteriolar dilation via CB1 receptors, resulting in a decreased GFR and an increased RBF without affecting MAP.