The potential therapeutic use of renin–angiotensin system inhibitors in the treatment of inflammatory diseases (original) (raw)
Related papers
Anti-inflammatory Role of Blocking the Renin-angiotensin System: Future Prospective
Al-Rafidain journal of medical sciences, 2022
The renin-angiotensin system (RAS) was thought to be in charge of managing blood pressure and electrolytes. It has been established that angiotensin II is also responsible for controlling inflammation in addition to blood pressure and potassium levels. Angiotensin converting enzyme 2 (ACE2), angiotensins (1-7), angiotensins (1-9), and other additional RAS components have been identified, and have anti-angiotensin II effects. Both angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) are utilized as anti-hypertensive medications and protecting the heart and kidneys, and counteract the part played by Ang II in the initiation of inflammation. This review provides crucial details that help explain how ACEI and ARBs reduce inflammation. Using reliable websites like Google Scholar, PubMed, and ResearchGate, the most recent publications were reviewed. Search terms have included "RAS role of Ang II in inflammation," "influence of ACEI," and "effect of ARBs on PPAR-gamma." The data were gathered from controlled clinical trials, in vitro studies, and animal-based studies; preprints, article reviews, and meta-analysis studies were excluded. Both ACEIs and ARBs reduce inflammation via a variety of mechanisms, which explains their cardioprotective and nephroprotective effects. They reduce inflammation by modulating an inflammatory pathway through either similar or dissimilar mechanisms.
A new concept for an old system: The anti-inflammatory paradigm of the renin-angiotensin system
Medical Hypotheses, 2009
The renin-angiotensin system (RAS) is classically known as a regulator of arterial pressure, which is accomplished by regulating the balance of water and sodium. This has led to the successful development of drugs such as anti-hypertensives that block the system. In addition, this system has a fundamental role in the mechanisms of inflammation and of defense for the cells and tissues of organisms. This last function is fulfilled by regulating oxidative stress at the cytoplasmic and mitochondrial level. From an evolutionary standpoint, this effect came before it began its role as a regulator of arterial pressure. If we were to consider cardiovascular disease as being inflammatory, then beyond its anti-hypertensive effect, RAS's blockade of this phenomenon could be seen as an etiologic treatment of cardiovascular disease.
The role of the renin-angiotensin system in the development of cardiovascular disease
The American Journal of Cardiology, 2002
A direct, continuous, and independent relation between blood pressure and the incidence of various cardiovascular events, such as stroke and myocardial infarction, is now well accepted. The increase in risk can be attributed to structural and functional changes in target organs. Central to many of these pathophysiologic processes is the renin-angiotensin system (RAS), specifically, angiotensin II. Binding of angiotensin II to angiotensin II type-1 (AT 1 ) receptors produces acute vasoconstriction, leading to an increase in blood pressure. AT 1 receptor activation also contributes independently to chronic disease pathology by promoting vascular growth and proliferation, and endothelial dysfunction. These negative consequences of angiotensin II are partly counteracted by angiotensin II type-2 (AT 2 ) receptor stimulation, which has favorable effects on tissue growth and repair processes. Thus, the use of selective AT 1 receptor antagonists in the treatment of hypertension has a 2-fold ratio-nale: (1) selective AT 1 receptor blockade targets the final common pathway for all major detrimental cardiovascular actions of angiotensin II, and (2) circulating angiotensin II levels (which increase during AT 1 receptor antagonist treatment) will be free to act only at unopposed AT 2 receptors, potentially providing additional end-organ protection. Angiotensin-converting enzyme (ACE) inhibitors interrupt the RAS by preventing the conversion of angiotensin I to angiotensin II. They also increase plasma levels of bradykinin, which possesses vasodilatory and tissue-protective properties. The combination of an AT 1 receptor antagonist with an ACE inhibitor represents an appealing therapeutic strategy, because it should produce more complete blockade of the RAS, while preserving the beneficial effects mediated by AT 2 receptor stimulation and increased bradykinin levels. ᮊ2002 by Excerpta Medica, Inc. Am J Cardiol 2002;89(suppl):3A-10A
Renin-angiotensin-aldosterone System Blockers, Hypertension, and Clinical Outcomes
Hypertension Journal
The renin-angiotensin (Ang)-aldosterone system (RAAS) consists of a group of enzymes and peptides whose main function is to control blood pressure (BP) by regulating vasoconstriction, sodium reabsorption and body fluid homeostasis. Historical Perspective Our knowledge of the RAAS started in 1898 when Tigerstedt and Bergman showed that renal extract from rabbits increased BP when infused and named it as renin. [1] In 1934, Goldblatt demonstrated that renal artery constriction caused renal ischemia and induced hypertension (HTN) in dogs. Later, in 1939-1940, Braun-Menende in Argentina and Page and Helmer in the USA simultaneously discovered a pressor substance capable of causing renal HTN. This was originally named hypertensin in Argentina and angiotonin in the USA and later renamed as angiotensin to give credit to both groups. [1] The discovery of captopril, an orally active Ang-converting enzyme inhibitor (ACE-I) in 1980 and Ang receptor blockers (ARBs) in 1998, went on to revolutionize medical care. [3] Current Understanding of the RAAS Pathway The modern view of the RAAS began with the concept that this was a lifesaving system, which raised BP in case of an acute hemorrhage. RAAS raises BP beginning with the release of renin into the bloodstream. [4] This circulating renin cleaves hepatic angiotensinogen and generates Ang I, which is converted to Ang II by pulmonary ACE. Ang II causes smooth muscle cell vasoconstriction, stimulates the sympathetic nervous system, and promotes renal retention of salt and water. Moreover, in the adrenal glands, Ang II stimulates the release of aldosterone, which enhances tubular sodium reabsorption in the kidney and increases the effective circulating plasma volume [Figure 1]. [4] In the heart, kidney, and brain, AII is also produced by non-ACE pathways namely chymases, cathepsin G, kallikreinlike enzymes and endopeptidases. [2] AII acts by binding to the G protein-coupled receptors type 1 (ATR1) and type 2 (ATR2). The ATR1 receptor mediates the more deleterious effects of AII-that is, vasoconstriction and cardiac and vascular hypertrophy. The ATR2 receptor regulates opposing effects. In addition to the conversion of AI to AII, ACE inactivates two vasodilator peptides, bradykinin and kallidin. [4]
Advantages of renin-angiotensin system blockade in the treatment of cardiovascular diseases
Medicinski arhiv, 2010
The renin angiotensin system (RAS) plays a key role in the regulation of cardiovascular function, with angiotensin II being involved in hemodynamic and non-hemodynamic mechanism in the pathophysiology of cardiovascular disease. A number of studies demonstrated that pharamacological modulation of the RAS, either with angiotensin converting (ACE) inhibitor or an angiotensin II receptor blocker (ARB), provides cardiovascular and renal protection. Blockade of the RAS, either with ACE inhibitors or ARBs, decreases cardiovascular morbidity and mortality in high risk patients. ACE inhibitors as well as ARBs are drugs of choice in congestive heart failure, as well as in diabetic nephropathy. Especially, the combined RAS blockade with ACE inhibitors and ARBs was more effective than monotherapy in diabetic or non-diabetic nephropathy with proteinuria. However, this combined RAS blockade was not equally dominant in treatment of hypertension and was not recommended for widespread antihypertensi...
The Renin-Angiotensin System in Cardiovascular and Renal Disease
High Blood Pressure & Cardiovascular Prevention, 2004
A variety of clinical and experimental studies have indicated that ACE inhibitors may improve insulin sensitivity and decrease Table II. Proposed mechanisms for the antidiabetic effects of RAS blockade Bradykinin/nitric oxide hypothesis Insulin signaling hypothesis Oxidative stress hypothesis Hemodynamic hypothesis Neurogenic hypothesis Adipocyte differentiation hypothesis
Rethinking the renin-angiotensin system and its role in cardiovascular regulation
Cardiovascular Drugs and Therapy, 2005
Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE 2 has been discovered. Both ACE and ACE 2 are emerging as key enzymes of the RAS, where ACE 2 may play a role as negative regulator of ACE. Moreover, ACE 2 appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE 2 , and their substrates and by-products are presently still unclear.
The American Journal of Cardiology, 2006
Inflammation is a key mechanism in the initiation, progression, and clinical sequelae of cardiovascular diseases (CVDs), including atherosclerosis, nephropathy, and cardiomyopathy. Angiotensin II, the major effector peptide of the renin-angiotensin-aldosterone system (RAAS), plays a significant role in the advent and perpetuation of these inflammatory diseases, most notably in atherogenesis. Consequently, suppression of the influence of angiotensin II by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce or potentially reverse atherosclerosis and other inflammation-associated CVDs. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors exert anti-inflammatory actions and prevent or reduce the development of atherosclerosis in animal models. Clinically, RAAS suppression reduces common carotid and femoral artery intima-media thickness, thus indicating moderation of the vascular disease process. These clinical benefits likely involve restraint of the deleterious effects of angiotensin II in addition to, or independent of, lowering blood pressure. Increasing evidence that the detection and monitoring of vascular inflammation are important tools in the management of atherosclerosis also implicates the RAAS in this pathogenic process. Inflammatory molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-␣, and C-reactive protein have potential diagnostic and prognostic values in CVD and are modified by angiotensinconverting enzyme inhibitors and angiotensin II receptor blockers. Monitoring these markers may be crucial for determining which agents, or combinations of agents, will result in the most clinically beneficial outcomes for patients. Large-scale trials are still required to determine the effects of the long-term suppression of inflammation on CVDs through the use of RAAS modulating agents, as well as to determine how closely markers of inflammatory activity may correlate with CVD outcomes.