Discovery and Characterization of Alamandine

Abstract

n the past few years, novel components of the renin-angiotensin system (RAS) have been described, including the prorenin/ renin receptor, 1 angiotensin-converting enzyme-2 (ACE2), 2,3 and Mas.4 ACE2 and Mas are now considered to be part of a novel axis of the RAS, the ACE2/angiotensin 1 to 7 [Ang-(1-7)]/Mas axis, 4-11 which counteracts most of the action of the classical Rationale: The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1-7).Objective: To characterize a novel component of the RAS, alamandine. Methods and Results:Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1-7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1-7), including vasodilation, antifibrosis, antihypertensive, and central effects. Key Words: angiotensin II ■ antihypertensive treatment ■ cardiovascular system ■ hypertension ■ renin-angiotensin system ■ vasoactive peptides ■ vascular reactivity Original received February 7, 2013; revision received February 22, 2013; accepted February 27, 2013. In January 2013, the average time from submission to first decision for all original research papers submitted to Circulation Research was 12.2 days.Brief UltraRapid Communications are designed to be a format for manuscripts that are of outstanding interest to the readership, report definitive observations, but have a relatively narrow scope. Less comprehensive than Regular Articles but still scientifically rigorous, BURCs present seminal findings that have the potential to open up new avenues of research. A decision on BURCs is rendered within 7 days of submission.From the

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

“…Contrarily, other reports have shown that AT2 deficiency does not affect Ang II-induced AAA in LDL -/-mice while PD123319 augments AAA through a mechanism that is AT2 receptor independent [59]. Such conflicting data could be explained by the different backgrounds of the used animals and the poor selectivity of PD123319, since this compound can also block the MrgD receptor for alamandine [60].…”

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“…Namely, Santos et al demonstrated that Ang-(1-7) is the ligand for the G-protein-coupled receptor Mas, and that the ACE2-Ang-(1-7)-Mas axis is the counter-regulating of the actions of classical RAS [4,5]. Also, a variety of biologically active peptides, novel components of the RAS have been found recently: proangiotensin-12 (angiotensin-(1-12)) [6], angiotensin A (Ang A) [7,8] and alamandine [9,10].…”

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“…By hydrolyzing the C-terminal amino acid of Ang A by ACE2, or decarboxylation of N-terminal aspartate of Ang-(1-7) into alanin, alamandine is produced [51]. Alamandine produced several biological effects including endothelial-dependent vasorelaxation in aortic rings of mice and rats or central cardiovascular effects.…”

“…Alamandine produced several biological effects including endothelial-dependent vasorelaxation in aortic rings of mice and rats or central cardiovascular effects. Microinjection of alamandine into rostal ventrolateral medulla (RVLM) increased blood pressure, and microinjection into caudal ventrolateral medulla (CVLM) decreased blood pressure, and modulated the baroreflex sensitivity after intra-cerebro ventricular (ICV) infusion [51]. Masrelated G-coupled receptor type D (MrgD) has been identified as the receptor for alamandine [51].…”