Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat.
Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat.
复制标题
前列腺素 E2 消除内皮素诱导的大鼠肾外髓质降血管直肠血管收缩。
DOI：
10.1172/jci117976
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Pallone,TL
中科院分区：
文献类型：
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作者：
Silldorff,EP;Yang,S;Pallone,TL
内皮素（ET）和前列腺素E2分别由集合管上皮细胞和间质细胞在髓质内合成。所有的升直血管（AVR）血液从内髓返回到外髓血管束中的皮质。我们推断激素可能通过扩散穿过AVR开窗调节外髓降直血管（OMDVR）的血管收缩来影响髓血流量。为了研究这种可能性，将从维管束解剖的OMDVR暴露于ET-1、2或3。每种内皮素亚型都能诱导稳定的血管收缩，ET-1 > ET-2 > ET-3（EC 50分别为1.8 x 10（-15）、5.9 x 10（-12）和8.8 x 10（-10）M）。ETA受体拮抗剂BQ-123和BQ-610（10（-6）M）以及ETA和ETB受体拮抗剂组合可减弱ET-1（10（-12）M）引起的血管收缩。BQ-123对ET-3（10（-8）M）的反应没有影响。ETB受体拮抗剂BQ-788（10（-6）M）可减弱ET-3（10（-10）M）的作用，但对ET-1（10（-12）M）无明显影响。最后，用ET-1（10（-10）M）或ET-3（10（-8）M）而不是ET-1（10（-10）M）可逆性扩张OMDVR。结论：ET-1、2、3是OMDVR的强收缩剂，ET-1主要通过ETA受体亚型介导，ET-3则通过ETB发挥作用。PGE 2调节ET诱导的收缩。这些发现与交互反馈和局部合成激素对髓质灌注的控制一致。图片
Endothelins (ET) and prostaglandin E2 are synthesized in the inner medulla by collecting duct epithelium and interstitial cells, respectively. All ascending vasa recta (AVR) blood returns from the inner medulla to the cortex in outer medullary vascular bundles. We reasoned that hormones might influence medullary blood flow by diffusing across AVR fenestrations to modulate vasoconstriction of outer medullary descending vasa recta (OMDVR). To investigate this possibility, OMDVR dissected from vascular bundles were exposed to ET-1, 2, or 3. Each endothelin isoform induced stable vasoconstriction with potency, ET-1 > ET-2 > ET-3 (EC50, 1.8 x 10(-15), 5.9 x 10(-12), and 8.8 x 10(-10) M, respectively). The ETA receptor antagonist BQ-123 and BQ-610 (10(-6) M), as well as an ETA and ETB receptor antagonist combination, attenuated vasoconstriction due to ET-1 (10(-12) M). BQ-123 had no effect on the response to ET-3 (10(-8) M). The ETB receptor antagonist BQ-788 (10(-6) M) attenuated the response to ET-3 (10(-10) M), but not that to ET-1 (10(-12) M). Finally, PGE2 (10(-6) M) reversibly dilated OMDVR preconstricted with ET-1 (10(-12) M) or ET-3 (10(-8) M) but not ET-1 (10(-10) M). We conclude that ET-1,2, and 3 are potent constrictors of OMDVR and the response to ET-1 is mainly ETA receptor subtype mediated, while ET-3 acts via the ETB. PGE2 modulates ET induced constriction. These findings are consistent with interactive feedback and control of medullary perfusion by locally synthesized hormones.Images