Journal of Invasive and Non-Invasive Cardiology

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Mini Review - Journal of Invasive and Non-Invasive Cardiology (2023) Volume 6, Issue 3

Reninââ?¬â??angiotensin system in the physiopathology of chronic diseases

Filippatos Krum *

Department of Cardiology, Nanjing Medical University, Nanjing, China,

*Corresponding Author:
Filippatos Krum
Department of Cardiology,
Nanjing Medical University
Nanjing, China
E-mail: krum.f@njmu.edu.cn

Received:31-May-2023, Manuscript No. AAINIC-23-9969;Editor assigned: 05-Jun-2023, PreQC No. AAINIC-23-99689(PQ);Reviewed:19-Jun-2023, QC No. AAINIC-23-99689;Revised:23-Jun-2023, Manuscript No. AAINIC-23-99689(R); Published:30-Jun-2023, DOI: 10.35841/aainic-6.3.155

Citation: Filippatos Krum. Renin–angiotensin system in the physiopathology of chronic diseases. J Invasive Non-invasive Cardiol. 2023;6(3):155

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Abstract

The Renin-Angiotensin System (RAS) is a complex regulatory pathway that plays a crucial role in maintaining blood pressure and electrolyte balance in the body. Dysregulation of this system has been implicated in the pathophysiology of several chronic diseases, including hypertension, heart failure, chronic kidney disease, and diabetes mellitus. Activation of the RAS can promote vasoconstriction, inflammation, fibrosis, and oxidative stress, leading to vascular dysfunction and end-organ damage. Therefore, targeting the RAS has become a cornerstone of the management of these chronic diseases, with drugs such as Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blockers (ARBs), and aldosterone antagonists widely used in clinical practice.

Introduction

The renin-angiotensin system (RAS) is a complex regulatory pathway that plays a crucial role in maintaining blood pressure and electrolyte balance in the body. Dysregulation of this system has been implicated in the pathophysiology of several chronic diseases, including hypertension, heart failure, chronic kidney disease, and diabetes mellitus. The RAS pathway begins with the release of renin from the juxtaglomerular cells of the kidneys. Renin cleaveangiotensinogen, a protein produced by the liver, to produce angiotensin I (Ang I). Ang I is then converted to angiotensin II (Ang II) by the angiotensin-converting enzyme (ACE), which is mainly located in the lungs but is also present in other organs such as the kidneys and the heart. Ang II exerts its effects by binding to the angiotensin type 1 receptor (AT1R), leading to vasoconstriction, aldosterone secretion, sodium and water retention, and increased sympathetic nervous system activity [1].

In chronic diseases, the RAS can become dysregulated, leading to increased Ang II levels and overactivation of the AT1R. This can promote vasoconstriction, inflammation, fibrosis, and oxidative stress, leading to vascular dysfunction and end-organ damage. For example, in hypertension, chronic activation of the RAS can lead to increased vascular resistance and endothelial dysfunction, leading to target organ damage in the heart, brain, and kidneys. In heart failure, the RAS can become overactivated due to decreased cardiac output and renal hypoperfusion. This leads to increased Ang II levels and activation of the AT1R, leading to vasoconstriction, sodium and water retention, and cardiac remodeling. This remodeling can lead to ventricular hypertrophy, fibrosis, and apoptosis, leading to further deterioration of cardiac function [2].

In chronic kidney disease, the RAS can also become dysregulated due to decreased renal function and increased renal hypoperfusion. This leads to increased Ang II levels and activation of the AT1R, leading to glomerular and tubular damage, proteinuria, and interstitial fibrosis. This fibrosis can lead to loss of renal function and end-stage renal disease. In diabetes mellitus, the RAS can become dysregulated due to hyperglycemia and insulin resistance. This leads to increased Ang II levels and activation of the AT1R, leading to endothelial dysfunction, inflammation, and renal damage. The RAS can also contribute to the development of diabetic retinopathy and neuropathy [

Therefore, targeting the RAS has become a cornerstone of the management of these chronic diseases, with drugs such as ACEIs, ARBs, and aldosterone antagonists widely used in clinical practice. These drugs can not only lower blood pressure but also reduce inflammation, fibrosis, and oxidative stress in the vascular and renal systems, leading to improved outcomes in these chronic diseases. However, the RAS is a complex system with multiple feedback loops and compensatory mechanisms, and the optimal strategy for targeting this system in chronic diseases remains an active area of research. Recent studies have identified novel targets, such as the angiotensin type 2 receptor (AT2R) and the Mas receptor, which have opposing effects to the AT1R and may have potential therapeutic benefits in chronic diseases. Moreover, personalized approaches, such as genetic testing and pharmacogenomics, could help identify patients who may benefit from specific RAS-targeted therapies [4].

Aldosterone antagonists, such as spironolactone and eplerenone, block the effects of aldosterone on its receptor, leading to a decrease in sodium and water retention and improved cardiac function. These drugs have been shown to reduce morbidity and mortality in patients with heart failure and reduced ejection fraction. However, these drugs are not without side effects. ACEIs and ARBs can cause hyperkalemia, renal dysfunction, and cough, while aldosterone antagonists can cause hyperkalemia and gynecomastia. In addition, long-term use of these drugs can lead to compensatory upregulation of the RAS, leading to decreased effectiveness over time [5].

Conclusion

The RAS plays a crucial role in the pathophysiology of several chronic diseases, including hypertension, heart failure, chronic kidney disease, and diabetes mellitus. Dysregulation of this system can promote vasoconstriction, inflammation, fibrosis, and oxidative stress, leading to end-organ damage. Therefore, targeting the RAS has become an important therapeutic strategy for managing these chronic diseases. The mainstay of RAS-targeted therapies includes ACEIs, ARBs, and aldosterone antagonists. These drugs have been shown to reduce morbidity and mortality in several large clinical trials, and are widely used in clinical practice.

 

References

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