The classical view of the renin-angiotensin system (RAS) is that of the circulating hormone pathway involved in salt and water homeostasis and blood pressure regulation. It is also involved in the pathogenesis of cardiac and renal disorders. This led to the creation of drugs blocking the actions of this classical pathway, which improved cardiac and renal outcomes. Our understanding of the RAS has significantly expanded with the discovery of new peptides involved in this complex pathway. Over the last two decades, a counter-regulatory or protective pathway has been discovered that opposes the effects of the classical pathway. Components of RAS are also implicated in the pathogenesis of obesity and its metabolic diseases. The continued discovery of newer molecules also provides novel therapeutic targets to improve disease outcomes. This article aims to provide an overview of an updated understanding of the RAS, its role in physiological and pathological processes, and potential novel therapeutic options from RAS for managing cardiorenal disorders, obesity, and related metabolic disorders.
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http://dx.doi.org/10.7759/cureus.40725 | DOI Listing |
Endogenous multiple modified LDL (mLDL) and the renin-angiotensin system play a significant role in the development of atherosclerosis. It has been found that by behavioral and hemodynamic parameters the physiological activity of angiotensin II (Ang II) in combination with mLDL is considerably modified due to weakening of its diuretic effect and the inversion of hypertensive and tachyarrhythmic effects. Atherosclerosis is a long-term pathological process, so a single administration of artificially synthesized Ang I-mLDL complexes can be considered a model of the first contact of the body with pathogenic factors.
View Article and Find Full Text PDFMed Oncol
January 2025
Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, Sichuan, China.
In the past decade, a variety of immune checkpoint inhibitors (ICIs) are currently approved for lung cancer in the world. As a new therapeutic approach, ICIs have shown significant clinical benefits in the first-line or second-line treatment for advanced lung cancer, improving the survival and quality of life of patients. Patients need to take multiple drugs in the meantime due to their own disease or side effects during treatment.
View Article and Find Full Text PDFDrug Discov Today
January 2025
Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan-333031, India. Electronic address:
Cardiorenal syndrome (CRS) is an interdependent dysfunction of the heart and kidneys, where failure in one organ precipitates failure in the other. The pathophysiology involves sustained renin-angiotensin-aldosterone-system (RAAS) activation, mitochondrial dysfunction, inflammation, fibrosis, oxidative stress and tissue remodeling, culminating in organ dysfunction. Existing therapies targeting the RAAS, diuretics and other agents have limitations, including diuretic resistance and compensatory sodium reabsorption.
View Article and Find Full Text PDFCureus
December 2024
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, JPN.
Background: The uremic toxin indoxyl sulfate (IS) is an important factor in chronic kidney disease (CKD) progression. Inhibitors of the renin-angiotensin system and add-on therapy with mineralocorticoid receptor (MR) antagonists can help reduce proteinuria and suppress CKD progression. However, the association between IS and MR activation remains unknown.
View Article and Find Full Text PDFOpen Heart
January 2025
Cardiology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia.
Background: Acute kidney injury (AKI) in the context of acute decompensated heart failure (ADHF) encompasses a broad spectrum of phenotypes with associated disparate outcomes. We evaluate the impact of 'ongoing AKI' on prognosis and cardiorenal outcomes and describe predictors of 'ongoing AKI'.
Methods: A prospective multicentre observational study of patients admitted with ADHF requiring intravenous furosemide was completed, with urinary angiotensinogen (uAGT) measured at baseline.
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