Vasoactive peptides: renin-angiotensin-aldosterone system

Nather, K., Loughrey, C. M. and Nicklin, S. A. (2019) Vasoactive peptides: renin-angiotensin-aldosterone system. In: Touyz, R. M. and Delles, C. (eds.) Textbook of Vascular Medicine. Springer: Cham, pp. 93-101. ISBN 9783030164805 (doi:10.1007/978-3-030-16481-2_9)

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Abstract

The classical renin-angiotensin-aldosterone system (RAAS) is characterized by formation of the effector peptide angiotensin II (Ang II) to participate in acute regulation of blood pressure (BP) and fluid and electrolyte balance. Ang II is generated through cleavage of angiotensinogen and angiotensin I by renin and angiotensin-converting enzyme (ACE), respectively. Ang II acts on two seven-transmembrane G protein-coupled receptors, the angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R), which mediate opposing actions via distinct signaling pathways. The AT1R mediates classical actions of Ang II including aldosterone secretion, vasoconstriction, renal sodium reabsorption and fluid retention, sympathetic activation, and stimulation of cardiac contractility, while the AT2R mediates vasodilation and natriuresis. A natural counter-regulatory RAAS axis acts through ACE2 to generate alternative peptides angiotensin-(1-7) and angiotensin-(1-9) which counteract classical RAAS actions. Furthermore, other RAAS peptide metabolites are also reported to have effects in the cardiovascular system. Pharmacological therapy focuses on inhibiting Ang II generation with ACE inhibitors (ACEi) and actions with AT1R blockers (ARBs). ACEi and ARBs reduce BP and alleviate end-organ damage in cardiovascular disease (CVD) and are mainstay treatments for hypertension and heart failure. The development of next-generation ACEi and ARBs focuses on the development of selective ACEi and biased ARBs and promises more selective and efficacious options for the treatment of CVD.

Item Type:Book Sections
Status:Published
Glasgow Author(s) Enlighten ID:Nicklin, Professor Stuart and Loughrey, Professor Christopher and Nather, Katrin
Authors: Nather, K., Loughrey, C. M., and Nicklin, S. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Publisher:Springer
ISBN:9783030164805
Published Online:03 August 2019

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