Current Pharmaceutical Design - Volume 19, Issue 17, 2013

The renin-angiotensin system hormone angiotensin II (Ang II) plays a central role in the pathophysiology of vasoconstriction, cardiovascular hypertrophy and hyperplasia. Two distinct subtypes of Ang II receptor, type 1 (AT1) and type 2 (AT2), have been identified, and both have been shown to belong to the G protein-coupled receptors (GPCRs) superfamily. AT1 and AT2 receptors may have antagonistic action. While th Read More

The octapeptide angiotensin II (Ang II) plays a homeostatic role in the regulation of blood pressure and water and electrolyte balance, and also contributes to the progression of cardiovascular remodeling. Ang II activates Ang II type 1 (AT1) receptor and type 2 (AT2) receptor, both of which belong to the seven-transmembrane, G protein-coupled receptor family. Most of the actions of Ang II such as promotion of cellular prolif Read More

Renin-angiotensin system (RAS) plays a key role in pathogenesis of cardiovascular disease and in the responsiveness for various types of medications. A large number of genetic investigations have been carried out to examine the association between gene variants of RAS and predisposition to cardiovascular diseases, such as hypertension, coronary artery disease and stroke. Even though the major results were Read More

Angiotensin II (Ang II) type 1 (ATl) receptor is a member of the G protein-coupled receptor superfamily and contains 359 amino acids. AT1 receptor blockers (ARBs, e.g., eprosartan, losartan, candesartan, valsartan, telmisartan, olmesartan, irbesartan, and azilsartan) have been developed and are available for clinical use, and basic and clinical studies have shown that ARBs are useful for preventing the development of cardiova Read More

Novokinin (RPLKPW) was designed based on ovokinin (FRADHPFL), a vasorelaxing peptide derived from ovalbumin. Novokinin relaxed a mesenteric artery isolated from the spontaneously hypertensive rat (SHR) at 10-5 M, and reduced SHR blood pressure at a dose of 0.1 mg/kg (po.) emulsified in 30% egg yolk. Novokinin exhibited an affinity for the AT2 receptor (Ki = 7 x 10-6M), and its antihypertensive and vasorelaxing activities Read More

The biological functions of angiotensin (Ang) II are mediated by two Ang II receptors, designated type 1 receptor (AT1R) and type 2 receptor (AT2R). Most of the cardiovascular effects of Ang II are mediated by AT1R that is expressed widely in the body. The expression of AT1R is up-regulated in cardiovascular lesions, and is regulated by many endogenous bioactive substances and drugs. The AT2R is generally consid Read More

Covalent modification of sulfur-containing amino acids in proteins by reactive oxygen species (ROS) has been attracting attention as a major post-translational modification regulating intracellular signal transduction pathways. Angiotensin II (Ang II), a major physiologically active substrate in renin-angiotensin (RAS) system, plays a central role in the pathophysiology of cardiovascular systems. Many evidences show that Ang II Read More

Current national guidelines have recommended the use of renin-angiotensin system inhibitors, including angiotensin II type 1 receptor blockers (ARBs), in preference to other antihypertensive agents for treating hypertensive patients with chronic kidney disease. However, the mechanisms underlying the renoprotective effects of ARBs are multiple and complex. Blood pressure reduction by systemic vasodilation with an ARB Read More

The Ang II type 1 receptor (AT1R)-associated protein (ATRAP/Agtrap) is a molecule specifically interacting with the carboxyl- terminal domain of AT1R. The results of in vitro studies showed that ATRAP suppresses Ang II-mediated pathological responses in cardiovascular cells by promoting AT1R internalization. With respect to the tissue distribution and regulation of ATRAP expression in vivo, ATRAP is broadly expressed in ma Read More

Recent evidence demonstrated that dysregulation of adipocytokine functions seen in abdominal obesity may be involved in the pathogenesis of the metabolic syndrome. Angiotensinogen, the precursor of angiotensin (Ang) II, is produced primarily in the liver, and also in adipose tissue, where it is up-regulated during the development of obesity and involved in blood pressure regulation and adipose tissue growth. Blockade of renin- Read More

For the past century, the renin–angiotensin system (RAS) has been recognized as one of the major blood pressure-regulating systems. Angiotensin II (Ang II) is the final physiologically active product of RAS, and it works not only as a strong vasopressor but also as a promotor of tissue remodeling in various organs such as heart, arteries, and kidneys. RAS is the predominant pathway of Ang II formation in human plasma, but not in t Read More

In the classical renin angiotensin system (RAS), angiotensin II (Ang II) plays many important roles in cardiovascular disease and in kidney, brain, and other organs via the Ang II type 1 receptor (AT⊂ 1). The RAS consists of many angiotensin peptides, including Ang (1-7), Ang (1-9), Ang (2-8), and Ang IV. Ang (1-7), produced by angiotensin-converting enzyme 2 (ACE2), has received attention because ACE2-deficient mice have heart Read More

Chymase, a chymotrypsin-like serine protease that is abundant in secretory granules from mast cells, has been identified to be a key enzyme in the local renin-angiotensin system (RAS) that generates angiotensin II (Ang II) independent of angiotensin converting enzyme (ACE). The pathophysiological significance of alternative Ang II-forming pathways in human cardiovascular disease remains controversial. Although Read More

The inverse association of cardiovascular risk with intake of omega-3 polyunsaturated fatty acids was suspected early in populations that are known to have a high consumption of fish and fish oil. Subsequent cohort studies confirmed such associations in other populations. Further evidence of possible beneficial effects on metabolism and cardiovascular health was provided by many studies that were able to show specific mech Read More

The clinically most relevant medications for lipid management are the statins, which constitute in the majority of the cases the basis of any lipid-modulating therapy. However, other agents are often needed to either reduce low-density cholesterol to target levels and/or to treat residual serum lipoprotein abnormalities. Niacin is currently the most potent available agent to increase high-density lipoprotein and reduce lipop Read More

Ezetimibe, an inhibitor of intestinal cholesterol absorption, can decrease total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TGs) and apolipoprotein (apo) B levels and increase high-density lipoprotein cholesterol (HDL-C) levels. Apart from lipid-lowering, ezetimibe may exert certain off-target actions (e.g. anti-inflammatory, anti-atherogenic and antioxidant) thus contributing to a further d Read More

Treatment with statins represents an essential component both of primary and secondary cardiovascular prevention strategies. However, a proportion of patients cannot reach low-density lipoprotein cholesterol (LDL-C) targets with the highest tolerable dose of a potent statin or is intolerant to statins. Several treatment options are available for these patients. Colesevelam is a relatively new bile acid sequestrant tha Read More

Dyslipidemia, and especially atherogenic dyslipidemia, a combination of small low-density lipoproteins cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) concentrations, represents a major cardiovascular (CV) risk factor. Nuclear receptor peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of lipid metabolism; PPAR ligands are used to treat dy Read More