(D-Pro⁷)-Angiotensin I/II (1-7) is a peptide antagonist of the Mas receptor, engineered by replacing the C-terminal Pro⁷ of Angiotensin-(1-7) with a D-proline[1]. The Mas receptor, a G-protein-coupled receptor for Ang-(1-7), elicits vasodilatory, anti-proliferative and anti-fibrotic protective signals upon activation[2]. (D-Pro⁷)-Angiotensin I/II (1-7) competitively blocks the binding of Angiotensin-(1-7) to Mas and is widely used to selectively interrupt ACE2/Ang-(1-7)/Mas-axis signaling in research[3].
In vitro, pretreatment of human pulmonary microvascular endothelial cells (PMVEC) with 100nM (D-Pro⁷)-Angiotensin I/II (1-7)(30min) completely abolished the protective effect of Ang-(1-7) against thrombin induced barrier disruption, reducing the trans-endothelial electrical resistance (TEER)[4]. In rat aortic vascular smooth muscle cells (VSMC) cultured in high glucose (25mM), 72h co-incubation with 1μM (D-Pro⁷)-Angiotensin I/II (1-7) reversed the inhibitory effect of Ang-(1-7) on high glucose-induced ErbB2 phosphorylation, restoring the p-ErbB2/t-ErbB2 ratio[5].
In vivo, (D-Pro⁷)-Angiotensin I/II (1-7) (10μM; 20min pre-incubation in isolated organ bath) reduced the maximal vasorelaxation evoked by Ang-(1-7) in rat renal arteries, completely blocking Ang-(1-7)-induced vasodilation and abolishing Ang-(1-7)-mediated activation of the NO-sGC-cGMP pathway[6]. (D-Pro⁷)-Angiotensin I/II (1-7) (0.1μM; 20min pre-incubation; vascular-bath perfusion) blocks an A-779-insensitive novel Ang-(1–7) receptor subtype and completely reverses the endothelium-dependent relaxation induced by Ang-(1–7) in isolated thoracic aortic rings from Sprague–Dawley rats[7].
References:
[1] Santos RA, Haibara AS, Campagnole-Santos MJ, et al. Characterization of a new selective antagonist for angiotensin-(1-7), D-pro7-angiotensin-(1-7). Hypertension. 2003;41(3 Pt 2):737-743.
[2] Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiol Rev. 2018;98(1):505-553.
[3] Santos RA, Frézard F, Ferreira AJ. Angiotensin-(1-7): blood, heart, and blood vessels. Curr Med Chem Cardiovasc Hematol Agents. 2005;3(4):383-391.
[4] Klein N, Gembardt F, Supé S, et al. Angiotensin-(1-7) protects from experimental acute lung injury. Crit Care Med. 2013;41(11):e334-e343.
[5] Akhtar S, Chandrasekhar B, Attur S, Dhaunsi GS, Yousif MH, Benter IF. Transactivation of ErbB Family of Receptor Tyrosine Kinases Is Inhibited by Angiotensin-(1-7) via Its Mas Receptor. PLoS One. 2015;10(11):e0141657.
[6] Yousif MHM, Benter IF, Diz DI, Chappell MC. Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity. Peptides. 2017;90:10-16.
[7] Silva DM, Vianna HR, Cortes SF, Campagnole-Santos MJ, Santos RA, Lemos VS. Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats. Peptides. 2007;28(3):702-707.
(D-Pro⁷)-Angiotensin I/II (1-7) 是一种Mas受体拮抗肽，通过将Angiotensin-(1-7) 的C端Pro⁷替换为D-型脯氨酸而设计[1]。Mas受体是 Ang-(1-7) 的G蛋白偶联受体，激活后可产生扩血管、抗增殖和抗纤维化的保护性信号[2]。(D-Pro⁷)-Angiotensin I/II (1-7) 竞争性阻断 Angiotensin-(1-7) 与Mas的结合，被广泛用于选择性阻断ACE2/Ang-(1-7)/Mas轴信号传导研究[3]。
在体外，100nM (D-Pro⁷)-Angiotensin I/II (1-7) 预处理人肺微血管内皮细胞（PMVEC）30分钟，可完全消除 Ang-(1-7) 对凝血酶诱导的屏障破坏的保护作用，使跨内皮电阻（TEER）降低[4]。在25mM高糖培养的大鼠主动脉血管平滑肌细胞（VSMC）中，与1μM (D-Pro⁷)-Angiotensin I/II (1-7) 共孵育72小时，可逆转 Ang-(1-7) 对高糖诱导的ErbB2磷酸化的抑制作用，恢复p-ErbB2/t-ErbB2比值[5]。
在体内，(D-Pro⁷)-Angiotensin I/II (1-7)（10μM；离体器官浴中预孵育20分钟）可减弱Ang-(1-7) 在大鼠肾动脉中诱导的最大舒张反应，完全阻断Ang-(1-7) 的血管舒张作用，并消除Ang-(1-7) 介导的NO-sGC-cGMP通路激活[6]。(D-Pro⁷)-Angiotensin I/II (1-7)（0.1μM；20分钟预孵育；血管浴灌注）可阻断一种对A-779不敏感的新型Ang-(1–7) 受体亚型，并完全逆转Ang-(1–7) 在Sprague–Dawley大鼠离体胸主动脉环中诱导的内皮依赖性舒张反应[7]。