Renin–angiotensin system

Renin–angiotensin system
Mikael Häggström · Public domain · source
Name	Renin–angiotensin system
Field	Nephrology; Cardiology; Endocrinology

Renin–angiotensin system The renin–angiotensin system is a hormonal network that regulates blood pressure, fluid balance, and electrolyte homeostasis. It integrates signals from the Kidney, Heart, Brain, Adrenal gland, and Lung to produce peptides and enzymes that alter vascular tone and renal function. Key discoveries were made during the 19th and 20th centuries by investigators associated with institutions such as the Johns Hopkins Hospital, the Harvard Medical School, and the University of Cambridge.

Overview and components

The system centers on the enzymatic cleavage of plasma substrates produced by organs including the Liver and the Kidney. Principal molecular components include the aspartyl protease renin, the decapeptide angiotensinogen, and the angiotensin-converting enzyme (ACE) predominantly expressed in pulmonary endothelium studied by researchers at the Pasteur Institute and the Karolinska Institute. Contemporary models also incorporate the angiotensin II peptide, angiotensin-(1–7), the Mas receptor, angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and the angiotensin-converting enzyme 2 (ACE2) characterized in structural studies at the Max Planck Society and the National Institutes of Health. Accessory proteins such as neprilysin, aminopeptidases, and chymases are noted in reviews from the World Health Organization panels and major textbooks authored by faculty at University of Oxford and Stanford University.

Physiology and mechanisms

Renin, a protease secreted by juxtaglomerular cells in the Kidney under influence from baroreceptors tied to afferent arteriolar pressure changes first investigated by groups at Mayo Clinic and Cleveland Clinic, cleaves angiotensinogen produced by hepatocytes in the Liver. The resulting angiotensin I is converted to angiotensin II by ACE in pulmonary endothelium, a pathway elucidated with biochemical methods developed at the Massachusetts Institute of Technology and the Scripps Research Institute. Angiotensin II acts via AT1R on vascular smooth muscle studied in laboratories at the University of California, San Francisco and the University College London, causing vasoconstriction, aldosterone release from the Adrenal gland described in clinical reports from Mount Sinai Hospital, and sodium reabsorption by renal tubules examined by teams at the Rockefeller University. Parallel pathways involving ACE2 and angiotensin-(1–7) signal through the Mas receptor to counterbalance vasoconstrictive effects; structural biology contributions from the European Molecular Biology Laboratory and the Cold Spring Harbor Laboratory clarified these ligand–receptor interactions.

Regulation and feedback control

Renin secretion is regulated by intrarenal baroreception, sympathetic nerve activation via β1-adrenergic receptors documented in experiments at the National University of Singapore and macula densa sensing of distal tubular sodium chloride investigated at the Weill Cornell Medicine and University of Toronto. Negative feedback occurs as angiotensin II suppresses further renin release, a principle reinforced in clinical trials coordinated by the European Society of Cardiology and the American Heart Association. Hormonal crosstalk includes natriuretic peptides from the Heart and corticosteroids from the Adrenal gland, with modulation by inflammatory mediators studied by groups at the Karolinska Institute and the Institut Pasteur.

Role in disease and pathology

Dysregulation of the system contributes to hypertension, heart failure, chronic kidney disease, and vascular remodeling; large outcome trials from the Framingham Heart Study, the ALLHAT investigators, and cohorts tracked by the Centers for Disease Control and Prevention documented epidemiologic links. Overactivation via AT1R promotes hypertrophy and fibrosis described in pathology reports from the Mayo Clinic and the Johns Hopkins Hospital, while deficient ACE2 activity has been implicated in acute lung injury and was examined during the SARS and COVID-19 pandemic by consortia including the World Health Organization and the National Institutes of Health. Genetic polymorphisms identified in populations studied by teams at the Wellcome Trust and the International HapMap Project associate with variable cardiovascular risk.

Pharmacology and therapeutic targeting

Pharmacologic modulation includes ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) developed by pharmaceutical collaborations involving firms such as Merck & Co., Pfizer, and AstraZeneca and evaluated in randomized controlled trials at centers like the Cleveland Clinic and the Brigham and Women's Hospital. Direct renin inhibitors, exemplified by aliskiren developed with industry partners, and neprilysin inhibitors combined with ARBs studied in the PARADIGM-HF trial led by investigators across the European Society of Cardiology network offer additional strategies. Monitoring and guidelines from the American College of Cardiology and the European Society of Cardiology shape clinical use, while adverse concerns such as hyperkalemia and renal function decline are managed following protocols from the National Kidney Foundation and regulators including the U.S. Food and Drug Administration.

Comparative and evolutionary aspects

Comparative studies reveal ancestral renin-like proteases in vertebrate lineages cataloged by researchers at the Smithsonian Institution and the Natural History Museum, London, with angiotensin peptides and receptors conserved across mammals, birds, and fish examined in evolutionary biology programs at the University of Cambridge and the Australian National University. Functional diversification, including the emergence of ACE2 and Mas receptor signaling, is framed by genomic analyses from the Human Genome Project and comparative genomics consortia such as the Ensembl and the 1000 Genomes Project, while ecological physiology work from the Scripps Institution of Oceanography and the Woods Hole Oceanographic Institution explores osmoregulatory roles in aquatic species.

Category:Endocrine system