RENAL MICROVASCULAR EFFECTS OF ENDOTHELIN
RENAL MICROVASCULAR EFFECTS OF ENDOTHELIN
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DOI：
10.1152/ajprenal.1990.259.2.f217
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发表时间：
1990-08-01
影响因子：
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通讯作者：
OHLSTEIN, EH
中科院分区：
文献类型：
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作者：
EDWARDS, RM;TRIZNA, W;OHLSTEIN, EH
检查内皮素 1、2 和 3（ET-1、-2、-3）对从兔肾解剖的单个传入和传出小动脉的管腔直径的影响。 ET-1 使两条小动脉的管腔直径产生浓度依赖性且持久的减小。 50% 最大响应 (EC50) 值为 1.4.+-。 0.41 和 0.9.+-。传入和传出小动脉分别为 0.65 nM。在传入小动脉中，ET-2 导致管腔直径减小（EC50 = 3.3 ± 1.75 nM），这与 ET-1 无法区分。然而，ET-3 的效力明显低于 ET-1 或 ET-2（EC50 = 21.9 ± 6.0 nM，P < 0.05）。在传出小动脉中获得了类似的结果，其中 ET-2 (0.25 .+-. 0.1 nM) 的 EC50 与 ET-1 相似，但 ET-3 的效力明显较低 (EC50 = 2.6 .+-. 0.4 nM, P < 0.05)。尼卡地平 (0.01-1 μM) 在传入小动脉中的 ET-1 浓度-反应曲线中产生浓度依赖性变化。维拉帕米(1μM)也引起ET-1反应曲线的显着变化。对 ET-1 的收缩反应对尼卡地平的敏感度显着高于对去甲肾上腺素的反应。相反，传出小动脉对 ET-1 和去甲肾上腺素的反应不受尼卡地平或维拉帕米的影响。结果表明，ET 是肾小球前和肾小球后微血管的有效血管收缩剂，可能在肾血流动力学的调节中发挥作用。尽管 ET-1 在传入小动脉中的收缩作用部分依赖于 Ca2+ 通过电位依赖性通道的进入，但 ET-1 对传出小动脉的作用似乎完全依赖于细胞内 Ca2+ 的动员或 Ca2+ 通过对二氢吡啶或苯烷基胺 Ca2+ 通道拮抗剂不敏感的通道的移动。
The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of individual afferent and efferent arterioles dissected from rabbit kidney were examined. ET-1 produced concentration-dependent and long-lasting decreases in lumen diameter in both arterioles. The 50% maximum response (EC50) values were 1.4 .+-. 0.41 and 0.9 .+-. 0.65 nM for afferent and efferent arterioles, respectively. In afferent arterioles, ET-2 produced decreases in lumen diameter (EC50 = 3.3 .+-. 1.75 nM) that were indistinguishable from ET-1. However, ET-3 was considerably less potent (EC50 = 21.9 .+-. 6.0 nM, P < 0.05) than ET-1 or ET-2. Similar results were obtained in the efferent arteriole in which the EC50 for ET-2 (0.25 .+-. 0.1 nM) was similar to ET-1, but ET-3 was significantly less potent (EC50 = 2.6 .+-. 0.4 nM, P < 0.05). Nicardipine (0.01-1 .mu.M) produced concentration-dependent shifts in the ET-1 concentration-response curve in afferent arterioles. Verapamil (1 .mu.M) also caused a significant shift in the ET-1 response curve. The contractile response to ET-1 was significantly more sensitive to nicardipine than was the response to norepinephrine. In contrast, the response of efferent arterioles to ET-1 and norepinephrine was unaffected by nicardipine or verapamil. The results demonstrate that ETs are potent vasoconstrictors of both the pre- and postglomerular microvasculature and may play a role in the regulation of renal hemodynamics. Although the contractile effects of ET-1 in the afferent arteriole are, in part, dependent on entry of Ca2+ through potential-dependent channels, the action of ET-1 on efferent arterioles appears to depend exclusively on mobilization of intracellular Ca2+ or the movement of Ca2+ through channels insensitive to dihydropyridine or phenylalkylamine Ca2+-channel antagonists.