Angiotensin and Related Peptides

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Introduction

The renin angiotensin system (RAS) is an important regulatory system for maintaining blood pressure, water and electrolyte balance, and cardiovascular homeostasis. Angiotensinogen is metabolized by renin to produce angiotensin I (AngI). Then AngI can be converted to angiotensin II (AngII) under the action of angiotensin-converting enzyme (ACE). It has been found that AngII is not the only biologically active molecule in angiotensin metabolites. Except for the well-known AngI (Ang_1-10), AngII (Ang_1-8), AngIII (Ang_2-8) and AngIV (Ang_3-8), there are many degradation products of angiotensin in the body, such as Ang_1-9, Ang_1-7, Ang_1-5, etc.

Mechanism of action

Among the members of angiotensin metabolism, AngI has only weak biological effect and is a substrate for a series of angiotensin hydrolysates. AngII exerts a variety of biological effects by binding to its specific AT1 and AT2 receptors, including strong vasoconstriction, elevation of hypertension, and promotion of vascular smooth muscle cell proliferation. In addition, AngII is responsible for the regulation vascular tone, the release of pro-inflammatory cytokines and the activation of the transcription factor NFκB. It inhibits the synthesis of nitric oxide (NO), and is widely involved in the pathogenesis of atherosclerosis, hypertension, congestive heart failure, and stroke.

Application of Angiotensins and Related Peptides

At present, the drugs targeting angiotensins and related peptides have been developed. For example, ACEI, the inhibitor of ACE and ARBs, is angiotensinII receptor blocker. Except for ACEI and ARBs, drugs for the downstream molecules of the RAS have made great contributions to the treatment of a variety of cardiovascular diseases, including essential hypertension, heart failure, etc. Recent studies have found that various metabolic peptides derived from angiotensinogen not only have relatively independent biological effects, but also that these different active fragments interact with each other in metabolic and biological effects. Understanding the relationship of the network regulation between angiotensin metabolism fragments helps to elucidate the mechanisms of cardiovascular disease and explore new targets for its prevention and treatment.

References

1. Ruiz-Ortega M, Lorenzo O, Suzuki Y, et al. Proinflammatory actions of angiotensins.[J]. Curr Opin Nephrol Hypertens, 2001, 10(3):321-329.
2. Kehoe P G. Angiotensins and Alzheimer's disease: a bench to bedside overview[J]. Alzheimers Research & Therapy, 2009, 1(1):3.