Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists
Angiotensin II type 2 receptors contribute to vascular responses in spontaneously hypertensive rats treated with angiotensin II type 1 receptor antagonists
复制标题
DOI：
10.1016/j.amjhyper.2004.11.007
复制
发表时间：
2005-04-01
影响因子：
3.2
通讯作者：
Volpe, M
中科院分区：
文献类型：
--
作者：
Cosentino, F;Savoia, C;Volpe, M
背景：血管紧张素II(Ang II)的收缩、增殖和氧化作用是由血管紧张素I型(Ang II type 1，AT 1)受体介导的。血管紧张素Ⅱ通过血管紧张素Ⅱ2型(AT(2))受体亚型(ATR)的作用还不是很清楚。越来越多的证据表明Ang II受体亚型之间存在串扰，AT(1)R阻断揭示了这一点。因此，在一定条件下，AT(2)R可能是AT(2)R的拮抗系统。方法：本研究旨在观察长期应用AT(1)R拮抗剂氯沙坦对自发性高血压大鼠(SHR)和Wistar-京都(WKY)大鼠胸主动脉AT(2)R介导的Ang II反应的影响。两组未经处理的动物均为对照组。结果：在去甲肾上腺素引起的收缩过程中，Ang II仅对长期服用氯沙坦(8周，30 mg/kg/d)的STIR大鼠的主动脉产生浓度依赖性的收缩作用。选择性AT(2)受体阻断剂PD123319、N-G-硝基-L-精氨酸甲酯(L-NAME)和B(2)受体拮抗剂HOE-140可抑制这些松弛。因此，血管紧张素转换酶II只有在治疗后的自发性高血压大鼠的主动脉中增加了一氧化氮(NO)的产生。AT(1)R阻断后，AT(2)R基因表达显著增加。这些结果表明，在高血压大鼠中，慢性AT(1)R阻断与血管紧张素转换酶II通过AT(2)R介导的NO产生的反向血管反应有关。结论：氯沙坦非掩蔽的AT(2)R血管松弛可显著促进AT，R阻断的有益的血管动力学效应。有鉴于此，我们的研究强调了整合的Ang II受体网络的重要性，这可能有助于进一步确定AT(1)受体阻滞剂良好的血管保护作用的机制。(C)2005年《美国高血压杂志》。
Background: Vasoconstrictive, proliferative and oxidative effects of angiotensin II (Ang II) are mediated by Ang II type 1 (AT,) receptors. The effects of Ang II via the Ang II type 2 (AT(2)) receptor subtype (ATR) are less well defined. Growing evidence shows the existence of crosstalk between the Ang II receptor subtypes, which is revealed by AT(1)R blockade. Hence, under certain conditions, AT(2)R may act as an antagonistic system with respect to the AT(2)R.Methods: The present study was designed to investigate the effects of long-term treatment with the AT(1)R antagonist losartan on the AT(2)R-mediated response to Ang II in thoracic aortas isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Untreated animals from both groups were used as controls. The mRNA expression of AT(1)R and AT(2)R was measured by reverse transcription-polymerase chain reaction.Results: During contraction in response to norepinephrine, Ang II induced concentration-dependent relaxation only in aortas isolated from STIR chronically treated with losartan (8 weeks; 30 mg/kg/day in drinking water). These relaxations were inhibited by the selective AT(2)R blocker PD123319, N-G-nitro-L-arginine methyl ester (L-NAME), and B(2)receptor antagonist HOE-140. Accordingly, nitric oxide (NO) production was increased by Ang II only in the aortas of treated SHR. After AT(1)R blockade, AT(2)R mRNA was significantly increased. These findings demonstrate that, in hypertensive rats, chronic AT(1)R blockade is associated with an inverted vasornotor response to Ang II via AT(2)R-mediated NO production.Conclusions: The losartan-unmasked AT(2)R-vasore-laxation could significantly contribute to the beneficial hernodynamic effects of AT,R blockade. In view of this, our study highlights the importance of the integrated Ang II receptor network, which may help to define further the mechanisms of the well-established vascular protective effects of AT(1)R blockers. (c) 2005 American Journal of Hypertension, Ltd.