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The Renin-Angiotensin System (RAS) is triggered by the cleavage of Angiotensinogen into multiple Angiotensin peptides by Renin, ACE/CD143, ACE-2, and other proteases. Angiotensin peptides regulate hemodynamics through wide ranging actions in the kidney, heart, vasculature, and sympathetic nervous system.
The Endothelin-1 peptide is formed from Big Endothelin by the converting enzymes ECE-1 and ECE-2. It is an extremely potent vasoconstrictor, and it increases cardiac output and cardiomyocyte proliferation. ET-1 signals through type A and type B Endothelin receptors.
In addition to Angiotensin and Endothelin, many vasoactive peptide hormones (e.g. natriuretic peptides, Bradykinin, Vasopressin) contribute to the central and peripheral regulation of blood pressure, vascular tone, and ion homeostasis.
Vascular reactivity is regulated by many classes of small molecules including eicosanoids (e.g. prostaglandins, leukotrienes, thromboxanes), purines, 5-HT/serotonin, histamine, and nitric oxide, plus adrenergic and cholinergic ligands. These molecules induce rapid vasoconstriction or relaxation of the vascular smooth muscle.