Enhanced renal angiotensin II subtype 1 receptor responses in the spontaneously hypertensive rat.
Enhanced renal angiotensin II subtype 1 receptor responses in the spontaneously hypertensive rat.
复制标题
自发性高血压大鼠肾血管紧张素 II 亚型 1 受体反应增强。
DOI：
10.1161/01.hyp.21.4.420
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Jackson,EK
中科院分区：
文献类型：
--
作者：
KostJr,CK;Jackson,EK
肾移植实验的结果表明，肾缺陷是导致自发性高血压大鼠（SHR）发生高血压的原因。此外，肾素-血管紧张素系统抑制剂的研究表明，血管紧张素 II (Ang II) 对于 SHR 高血压的发生和维持是必需的。这些观察结果促使我们提出这样的假设：这些大鼠的高血压是由于肾脏对 Ang II 的反应性增强所致。本研究的目的是确定成年（12 至 14 周龄）SHR 相对于 Wistar-Kyoto 对照大鼠是否存在肾对 Ang II 的增强反应。为了防止 SHR 中高血压引起的肾功能变化，我们从 4 周龄起通过长期卡托普利治疗（每天 100 mg/kg）将两种菌株维持在正常血压状态。与 Wistar-Kyoto 大鼠相比，肾内 Ang II 输注引起 SHR 肾血流量和肾小球滤过率显着更大程度的下降，以及肾血管阻力显着更大程度的增加。 DuP 753（Ang II 亚型 1 [AT1] 受体拮抗剂）而非 PD 123177（Ang II 亚型 2 受体拮抗剂）阻断 SHR 中肾脏对 Ang II 的反应，表明肾脏对 Ang II 反应的增强仅由 AT1 受体亚型介导。与肾脏对 Ang II 的反应不同，两种菌株的肾脏对动脉周围肾神经刺激的反应相似，表明 SHR 中肾脏对 Ang II 选择性高反应，而不是对所有血管收缩剂普遍高反应。从这些对长期接受卡托普利治疗的大鼠进行的研究中，我们得出结论：1) SHR 具有遗传决定的、增强的肾脏对 Ang II 的反应性； 2) 肾脏对Ang II的反应性增强是由AT1受体介导的； 3)肾脏对动脉周围神经刺激的反应没有显着增强，表明SHR肾脏对Ang II有选择性高反应性。
Results from renal transplantation experiments demonstrate that a renal defect is responsible for the development of hypertension in the spontaneously hypertensive rat (SHR). In addition, studies with inhibitors of the renin-angiotensin system have shown that angiotensin II (Ang II) is required for the development and maintenance of hypertension in the SHR. These observations prompted us to propose the hypothesis that hypertension in these rats is due to an enhanced renal responsiveness to Ang II. The purpose of the present study was to determine whether an enhanced renal responsiveness to Ang II exists in adult (12- to 14-week-old) SHR relative to Wistar-Kyoto control rats. To prevent hypertension-induced changes in renal function in SHR, we maintained both strains in the normotensive state from 4 weeks of age with long-term captopril treatment (100 mg/kg per day). Intrarenal Ang II infusions induced a significantly greater decrease in renal blood flow and glomerular filtration rate and a significantly greater increase in renal vascular resistance in SHR compared with Wistar-Kyoto rats. DuP 753 (Ang II subtype 1 [AT1] receptor antagonist), but not PD 123177 (Ang II subtype 2 receptor antagonist), blocked the renal responses to Ang II in SHR, suggesting that the enhanced renal responsiveness to Ang II was mediated solely by the AT1 receptor subtype. Unlike renal responses to Ang II, renal responses to periarterial renal nerve stimulation were similar in both strains, suggesting a selective renal hyperresponsiveness to Ang II in the SHR rather than a general hyperresponsiveness toward all vasoconstrictors. From these studies in chronically captopril-treated rats, we conclude that 1) SHR have a genetically determined, enhanced renal responsiveness to Ang II; 2) the enhanced renal responsiveness to Ang II is mediated by the AT1 receptor; and 3) renal responses to periarterial nerve stimulation are not significantly enhanced, suggesting a selective hyperresponsiveness to Ang II in the kidneys of SHR.