Stegbauer Johannes, Oberhauser Vitus, Vonend Oliver, Rump Lars Christian
Department of Internal Medicine I, Marienhospital Herne, Ruhr-University Bochum, Hölkeskampring 40, D-44625 Herne, Germany.
Cardiovasc Res. 2004 Feb 1;61(2):352-9. doi: 10.1016/j.cardiores.2003.11.017.
Angiotensin (Ang)-(1-7) generated from Ang I and II is reported to act as an endogenous angiotensin-converting enzyme (ACE) inhibitor and angiotensin type 1 (AT1)-receptor antagonist in vitro and in vivo. Ang-(1-7) has been suggested to play an important role in hypertension.
Therefore, we tested whether Ang-(1-7) differentially modulates vascular resistance and neurotransmission in isolated kidneys of spontaneously hypertensive rats stroke prone (SHR-SP) and Wistar-Kyoto rats (WKY). Ang-(1-7) was administered in three concentrations (0.1, 1 and 10 micromol/l) to prevent Ang I- and Ang II-induced pressor responses and facilitation of noradrenaline release. There were indeed concentration-dependent strain differences. Ang-(1-7) prevented Ang I- and Ang II-mediated changes in vascular resistance more potently in SHR-SP than in WKY by inhibiting ACE and by blocking AT1-receptors. Ang-(1-7) by itself had no influence on renal vascular tone in both strains. Ang-(1-7) inhibited Ang I-mediated facilitation of noradrenaline release more potently than Ang II-mediated facilitation of noradrenaline release. Ang-(1-7) by itself enhanced noradrenaline release from SHR-SP, but not from WKY kidneys.
Ang-(1-7) had a greater impact on Ang I and Ang II modulation of renal vascular resistance in SHR-SP than in normotensive rats. Furthermore, Ang-(1-7) by itself has facilitatory presynaptic effects on noradrenaline release but no postsynaptic effects on renal vascular resistance in SHR-SP. Since plasma levels of Ang-(1-7) accumulate during ACE-inhibitor or AT1-receptor antagonist therapy, Ang-(1-7) could contribute to antihypertensive effects of these agents.
据报道，由血管紧张素（Ang）-I和II生成的Ang-(1-7)在体内外可作为内源性血管紧张素转换酶（ACE）抑制剂和血管紧张素1型（AT1）受体拮抗剂。Ang-(1-7)被认为在高血压中起重要作用。
因此，我们测试了Ang-(1-7)是否对易发生中风的自发性高血压大鼠（SHR-SP）和Wistar-Kyoto大鼠（WKY）的离体肾脏中的血管阻力和神经传递有不同的调节作用。以三种浓度（0.1、1和10微摩尔/升）给予Ang-(1-7)，以预防Ang I和Ang II诱导的升压反应以及去甲肾上腺素释放的促进作用。确实存在浓度依赖性的品系差异。通过抑制ACE和阻断AT1受体，Ang-(1-7)在SHR-SP中比在WKY中更有效地预防了Ang I和Ang II介导的血管阻力变化。Ang-(1-7)本身对两种品系的肾血管张力均无影响。Ang-(1-7)比Ang II介导的去甲肾上腺素释放促进作用更有效地抑制了Ang I介导的去甲肾上腺素释放促进作用。Ang-(1-7)本身增强了SHR-SP肾脏中去甲肾上腺素的释放，但未增强WKY肾脏中去甲肾上腺素的释放。
与正常血压大鼠相比，Ang-(1-7)对SHR-SP中肾血管阻力的Ang I和Ang II调节作用影响更大。此外，Ang-(1-7)本身对SHR-SP中去甲肾上腺素释放有突触前促进作用，但对肾血管阻力无突触后作用。由于在ACE抑制剂或AT1受体拮抗剂治疗期间Ang-(1-7)的血浆水平会累积，因此Ang-(1-7)可能有助于这些药物的降压作用。
