Autoradiographic identification of kidney angiotensin IV binding sites and angiotensin IV-induced renal cortical blood flow changes in rats
Autoradiographic identification of kidney angiotensin IV binding sites and angiotensin IV-induced renal cortical blood flow changes in rats
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DOI：
10.1016/s0196-9781(97)00291-x
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发表时间：
1998-01-01
期刊：
影响因子：
3
通讯作者：
Wright, JW
中科院分区：
文献类型：
--
作者：
Coleman, JKM;Krebs, LT;Wright, JW
本研究利用体外放射自显影技术，初步确定六肽血管紧张素 TV (AngIV) 的特异性结合位点存在于大鼠肾皮质和外髓质中，但不存在于内髓质中。该结合位点被称为 AT(4)，与之前表征的 AT 和 AT 位点不同，并且不结合特定的 AT(1) 受体拮抗剂 DuP753 或 AT(2) 受体拮抗剂 PD123177。肾动脉输注 AngIV 会导致皮质血流量呈剂量依赖性增加，而不会改变全身血压。相比之下，输注血管紧张素 II (AngII) 会导致皮质血流量急剧减少，同时全身血压显着升高。 [D-Val(1)]AngIV（一种不与 AT(4) 受体位点结合的类似物）以及对该位点具有较低亲和力的 C 端截短的类似物 AngIV (1-4) 和 AngIV (1-5) 的输注不会对皮质血流产生任何变化。 [Nle(1)]AngIV 和 [Lys(1)]AngIV 类似物以高亲和力结合在 AT(4) 受体位点，输注可增加皮质血流量，但对血压没有影响。用特定的 AT(4) 受体拮抗剂 Divalinal-AngIV 进行预处理，完全阻断 AngIV 诱导的血流升高，但未能影响 AngII 诱导的血流减少，表明这些配体作用于不同的受体位点。用一氧化氮合酶抑制剂 N-G-单甲基-L-精氨酸进行预处理，也能阻止随后 AngIV 诱导的皮质血流量增加。这些数据支持AngIV通过AT(4)受体亚型对肾血流动力学产生独特影响的观点，并表明AngIV诱导的血流升高可能是由一氧化氮介导的。 (C) 1998 爱思唯尔科学公司。
The present investigation initially determined that specific binding sites for the hexapeptide angiotensin TV (AngIV) are present in the rat kidney cortex and outer medulla but not in the inner medulla, using in vitro autoradiographic techniques. This binding site has been termed AT(4), is distinct from the previously characterized AT, and AT, sites, and does not bind the specific AT(1) receptor antagonist DuP753 or the AT(2) receptor antagonist PD123177. Renal artery infusions of AngIV produced a dose-dependent increase in cortical blood flow without altering systemic blood pressure. In contrast, the infusion of angiotensin II (AngII) induced a dramatic decrease in cortical blood flow, accompanied by a significant elevation in systemic blood pressure. The infusion of [D-Val(1)]AngIV, an analog that does not bind at the AT(4) receptor site, and the C-terminal truncated analogs AngIV (1-4) and AngIV (1-5) that possess lower affinity for this site, produced no change in cortical blood flow. The infusion of [Nle(1)]AngIV and [Lys(1)]AngIV, analogs that bind with high affinity at the AT(4) receptor site, produced increases in cortical blood flow with no influence on blood pressure. Pretreatment with a specific AT(4) receptor antagonist, Divalinal-AngIV, completely blocked AngIV-induced elevations in blood flow, but failed to influence AngII-induced decreases in blood flow, suggesting that these ligands are acting at different receptor sites. Pretreatment with the nitric oxide synthase inhibitor, N-G-Monomethyl-L-Arginine, also blocked subsequent AngIV-induced increases in cortical blood flow. These data support the notion that AngIV exerts a unique influence upon renal hemodynamics via the AT(4) receptor subtype, and suggest that AngIV-induced elevations in blood flow may be mediated by nitric oxide. (C) 1998 Elsevier Science Inc.