Vascular responses to endothelin-1, angiotensin-II, and U46619 in glycerol-induced acute renal failure.
Vascular responses to endothelin-1, angiotensin-II, and U46619 in glycerol-induced acute renal failure.
复制标题
甘油诱导的急性肾衰竭中血管对内皮素-1、血管紧张素-II 和 U46619 的反应。
DOI：
10.1097/00005344-200110000-00009
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发表时间：
2001
影响因子：
3
通讯作者：
Oyekan,AO
中科院分区：
文献类型：
--
作者：
Newaz,MA;Oyekan,AO
血管紧张素II和内皮素-1是急性肾功能衰竭（ARF）的主要内源性血管收缩剂，它们可以相互调节作用。本研究旨在通过评估这些血管收缩剂在各自拮抗剂存在下在离体灌注肾中的作用，来评估它们在甘油诱导的ARF中的相互作用。在ARF中，血管紧张素II （2.5 ~ 25 ng）引起灌注压升高。非选择性血管紧张素受体拮抗剂Saralasin （1 μM）可使这些反应降低61±6%（p< 0.05）。令人惊讶的是，选择性PGH 2/血栓素a2受体阻断剂SQ29548, 1 μM也能降低血管紧张素II的反应（62±4%;p< 0.05）。ET a选择性受体拮抗剂BQ610 1 μM与ET b选择性受体拮抗剂BQ788 1 μM相比，作用减弱70±4%（p< 0.05）。在ARF中，与血管紧张素II相比，内皮素-1 （5-25 ng）的血管收缩作用减弱。Saralasin进一步降低内皮素-1反应65±2%(p< 0.05)，而SQ29548则无作用。BQ788降低应答率为67±7%(p< 0.05)， BQ610无应答率为42±30% （p< 0.05）。BQ610和BQ788联合用药可进一步降低血管收缩89±3%（p< 0.05）。ARF中对U46619的响应没有改变。然而，saralasin和BQ788能减弱其血管收缩作用，而BQ610不能。我们得出结论，ARF的血管反应可能归因于通过激活ET B和/或PGH 2/血栓素a2受体对血管紧张素II的反应增强。我们还认为，ARF中血管收缩对内皮素-1的反应主要是ET B受体介导的。
Angiotensin II and endothelin-1, major endogenous vasoconstrictors in acute renal failure (ARF), can modulate the effects of each other. This study aimed to evaluate the interaction between these vasoconstrictors in glycerol-induced ARF by evaluating their effects in the isolated perfused kidney in the presence of their respective antagonists. In ARF, angiotensin II (2.5–25 ng) caused an increase in perfusion pressure. Saralasin, 1 μM, a nonselective angiotensin receptor antagonist, reduced these responses by 61±6%(p< 0.05). Surprisingly, SQ29548, 1 μM, a selective PGH 2/thromboxane A 2 receptor blocker, also reduced angiotensin II responses (62±4%; p< 0.05). BQ610 1 μM, an ET A-selective receptor antagonist, was without effect, but BQ788 1 μM, an ET B-selective antagonist, attenuated the response by 70±4%(p< 0.05). In ARF, in contrast to angiotensin II, vasoconstriction by endothelin-1 (5–25 ng) was diminished. Saralasin further attenuated endothelin-1 response by 65±2%(p< 0.05), whereas SQ29548 was without effect. BQ788 reduced the responses by 67±7%(p< 0.05), whereas BQ610 was without effect (42±30%; p> 0.05). BQ610 and BQ788 combination further reduced vasoconstriction by 89±3%(p< 0.05). Responses to U46619 were not changed in ARF. However, saralasin and BQ788, but not BQ610, attenuated its vasoconstrictor action. We conclude that vascular responses in ARF may be attributed to enhanced responses to angiotensin II through activation of ET B and/or PGH 2/thromboxane A 2 receptors. We also suggest that the vasoconstrictor response to endothelin-1 in ARF is predominantly ET B receptor-mediated.