Katovich Michael J, Grobe Justin L, Raizada Mohan K
Department of Pharmacodynamics, University of Florida, PO Box 100487, J. Hillis Miller Health Science Center, Gainesville, FL 31610-0487, USA.
Curr Hypertens Rep. 2008 Jun;10(3):227-32. doi: 10.1007/s11906-008-0043-9.
Over the past two decades, enormous progress has been made in understanding the possible physiological significance of alternate renin-angiotensin system processing pathways and angiotensin fragments, such as angiotensin (Ang)-(1-7). Evidence from in vivo and ex vivo studies in humans and various animal models suggests a possible role for this heptapeptide in blood pressure regulation, although the mechanisms involved are most likely indirect, involving some combination of bradykinin and nitric oxide signaling. In contrast, a growing body of in vivo and in vitro evidence supports direct cardioprotective (antihypertrophic, antifibrotic) actions of Ang-(1-7). Here, we review key studies investigating the blood pressure and tissue-protective roles of Ang-(1-7), and summarize potential genomic and pharmacologic therapeutic strategies previously advanced by our group and others.
在过去二十年中,我们在理解肾素 - 血管紧张素系统替代加工途径和血管紧张素片段(如血管紧张素(Ang)-(1-7))可能的生理意义方面取得了巨大进展。来自人体和各种动物模型的体内和体外研究证据表明,这种七肽在血压调节中可能发挥作用,尽管其涉及的机制很可能是间接的,涉及缓激肽和一氧化氮信号传导的某种组合。相比之下,越来越多的体内和体外证据支持Ang-(1-7)的直接心脏保护作用(抗肥厚、抗纤维化)。在此,我们回顾了研究Ang-(1-7)血压和组织保护作用的关键研究,并总结了我们小组和其他研究小组先前提出的潜在基因组和药物治疗策略。