The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats.
The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats.
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DOI：
10.1172/jci119531
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发表时间：
1997-07
期刊：
影响因子：
--
通讯作者：
H. Siragy;Robert M. Carey
中科院分区：
文献类型：
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作者：
H. Siragy;Robert M. Carey
血管紧张素AT2受体调节肾脏产生环鸟苷3‘，5’-单磷酸(cGMP；J.投资。1996年。97：1978-1982)。在目前的研究中，我们假设血管紧张素II(Ang II)作用于AT2受体，刺激肾脏一氧化氮的产生，导致先前观察到的cGMP增加。采用微透析技术，观察在低钠平衡或正常钠平衡状态下，静脉注射血管紧张素Ⅱ受体拮抗剂PD-123319(PD)、血管紧张素Ⅱ受体拮抗剂氯沙坦、一氧化氮合酶抑制剂硝基-精氨酸甲酯(-NAME)、神经一氧化氮合酶特异性抑制剂7-硝基吲唑(7-NI)或血管紧张素转换酶II(Ang II)对清醒大鼠肾间质液cGMP的影响。钠耗竭显著增加RIF、cGMP。钠耗竭时，PD和-NAME均引起RIF cGMP类似的下降。联合应用PD和-NAME可将RIF cGMP降低到单独使用PD或-NAME或在正常钠摄入时观察到的水平。在正常钠摄入量期间，Ang II导致RIF cGMP增加两倍。无论是PD还是-NAME，无论是单独还是联合，都不会改变RIF cGMP。Ang II与PD或-NAME合用后，RIF cGMP较单独应用Ang II时显著降低。联合应用Ang II、PD和-NAME可阻断Ang II单独产生的RIF cGMP的增加。钠耗竭时，7-NI降低RIF cGMP，但PD单独作用或PD与7-NI联合作用时，cGMP下降幅度大于7-NI单独作用。在正常钠摄入量下，7-NI可阻断Ang II诱导的RIF cGMP升高。PD单独或与7-NI合用比单独使用7-NI对cGMP的抑制作用更强。钠耗竭时，7-NI(部分)和-NAME(完全)抑制RIF对-精氨酸的cGMP反应。这些数据表明，钠耗竭时肾素-血管紧张素系统的激活通过血管紧张素AT2受体上的血管紧张素II刺激增加了肾脏一氧化氮的产生。这一反应部分是由神经型一氧化氮合酶介导的，但其他一氧化氮合酶亚型也通过这一途径参与一氧化氮的产生。
The angiotensin AT2 receptor modulates renal production of cyclic guanosine 3',5'-monophosphate (cGMP; J. Clin. Invest. 1996. 97:1978-1982). In the present study, we hypothesized that angiotensin II (Ang II) acts at the AT2 receptor to stimulate renal production of nitric oxide leading to the previously observed increase in cGMP. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) cGMP in response to intravenous infusion of the AT2 receptor antagonist PD 123319 (PD), the AT1 receptor antagonist Losartan, the nitric oxide synthase (NOS) inhibitor nitro--arginine-methyl-ester (-NAME), the specific neural NOS inhibitor 7-nitroindazole (7-NI), or Ang II individually or combined in conscious rats during low or normal sodium balance. Sodium depletion significantly increased RIF cGMP. During sodium depletion, both PD and -NAME caused a similar decrease in RIF cGMP. Combined administration of PD and -NAME decreased RIF cGMP to levels observed with PD or -NAME alone or during normal sodium intake. During normal sodium intake, Ang II caused a twofold increase in RIF cGMP. Neither PD nor -NAME, individually or combined, changed RIF cGMP. Combined administration of Ang II and either PD or -NAME produced a significant decrease in RIF cGMP compared with that induced by Ang II alone. Combined administration of Ang II, PD, and -NAME blocked the increase in RIF cGMP produced by Ang II alone. During sodium depletion, 7-NI decreased RIF cGMP, but the reduction of cGMP in response to PD alone or PD combined with 7-NI was greater than with 7-NI alone. During normal sodium intake, 7-NI blocked the Ang II-induced increase in RIF cGMP. PD alone or combined with 7-NI produced a greater inhibition of cGMP than did 7-NI alone. During sodium depletion, 7-NI (partially) and -NAME (completely) inhibited RIF cGMP responses to -arginine. These data demonstrate that activation of the renin- angiotensin system during sodium depletion increases renal nitric oxide production through stimulation by Ang II at the angiotensin AT2 receptor. This response is partially mediated by neural NOS, but other NOS isoforms also contribute to nitric oxide production by this pathway.