Introduction
Organic nitrates (ORNs) have been used for the prevention and treatment of myocardial ischemia and angina pectoris for approximately 130 years. They are polyolesters of nitric acid (RONO2) that can be classified into two categories: high potency ORNs that contain three or four nitrate groups, such as nitroglycerin (NTG) and pentaerythritol tetranitrate (PETN); low potency ORNs containing one or two nitrate groups, for instance, isosorbide dinitrate (ISDN), isosorbide-2-mononitrate (IS-2-MN), isosorbide-5-mononitrate (IS-5-MN), and nicorandil (Munzel et al., 2005). ORNs are bioactivated to produce nitric oxide (NO) by various enzymes, including cytochrome P450 (CYPs), xanthine oxidase (XO), glutathione-S-transferases (GSTs), aldehyde dehydrogenases (ALDHs), and so on (Table 1). Released NO activates soluble guanylyl cyclase (sGC), which converts guanosine-5’-triphosphate (GTP) to 3’, 5’-cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells. Elevated intracellular cGMP inhibits the entry of calcium into the cell, and hence causing smooth muscle relaxation and vasodilation. Therefore, ORNs’ vasodilatory effect is coupled to their metabolism in vascular smooth muscle. NO acts predominantly on venous capacitance vessels, thereby reduces venous pressure and ventricular preload, which decrease myocardial wall tension and oxygen demand by heart (Munzel and Gori, 2013).
Although several enzymes have been identified to metabolize and bioactivate ORNs, the corresponding mechanisms still remain incompletely understood, especially regarding the precursor of NO and the link between NO and activation of sGC. Investigation of these hurdles were impeded by limited tools to measure labile reaction intermediates (e.g. OR...
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...oic acid (Packer et al., 1987; Watanabe et al., 1998b; Watanabe et al., 1998a; Gori et al., 2001; Dudek et al., 2008). Additionally, inducer of ALDH2, ALDA-1, has been shown to prevent tolerance and minimize cardiac damage via increasing ALDH2 level (Chen et al., 2008).
Conclusions
Organic nitrates have been served as the exogenous source of nitric oxide and an excellent therapeutic agent for various cardiovascular diseases for more than a century. Although they are rapid acting and relatively safe, chronic application of ORNs induces pharmacological tolerance and endothelial dysfunction. Investigation of the metabolism (bioactivation and clearance) of ORNs has allowed us understand the underlying mechanisms of NO generation, tolerance, and potential toxic effects, and therefore provide corresponding avoidance strategies and extend the use of this powerful agent.
Nitric oxide is a gaseous, diatomic molecule that plays an important role as a mediator of cardiac function, working largely as a vasodilator in the cardiovascular system. Nitric oxide is synthesized by a family of enzymes known as nitric oxide synthases (...
Hegab Z, Gibbons S, Mamas M, et al. Role of advanced glycation end products in cardiovascular disease. World J Cardiol. 2012 Apr; 4 (4): 20-102.
There are various treatments for acute coronary syndrome to prevent the occurrence of an acute myocardial infarction. The purpose of this essay is to discuss the current research of the pharmacological treatments of this condition and to evaluate the relevance of this research in relation to the practise of paramedics.
Its ability to inhibit phosphodiestarase type 1 leading to an increase in the concentration of cyclic AMP which is thought to result in its vasodilator effects
...on and forms an inhibitory complex with caveolin-1 leads to decrease in activity of enzyme in the cells. Transcription of Cav-1 gene is regulated by cholesterol responsive elements. Exposure of fibroblast and endothelial cells to free cholesterol and LDL Cholesterol was found to up regulate Cav-1 expression. Ca+2 mobilizing agents cause disinhibiton of e NOS by promoting Ca+2/Calmodulin triggered dissociation of Cav-1.
... had a higher induction effect on HBD1 than their counterpart at the same concentration (Figure 3). While on LL-37, 5-phenyl valeric acid (C5), 6-phenyl hexanoic acid (C6) and 7-phenyl heptanic acid (C7) had a higher response than their fatty acids, the peak expression observed at 5-phenyl valeric acid (C5) (Figure 3).
Atherosclerosis is a disease in which plaque builds up inside the arteries. Arteries are blood vessels that carry oxygen-rich blood to the heart and other parts of your body. It develops by the accumulation of excess Low Density Lipoprotein (LDL) in the arterial wall causing damage to the vascular endothelium which increases expression of adhesion molecules that latch onto monocytes and T cells and decreases the ability of the endothelial cells to release Nitric oxide (NO). Monocytes and LDL accumulates at the site of injury then penetrates the intima where monocytes differenciate to become macrophages and the ...
Cardiovascular disease is currently the nation’s leading non-communicable cause of morbidity and mortality. According to the American Heart Association, the most common form of cardiovascular disease is coronary artery disease, a condition in which the heart’s blood supply is reduced due to a narrowing of the coronary arteries. These arteries play a significant role in regulating the flow of oxygenated blood to the heart. As blood circulates through the arteries, it exerts a force against the vessel walls, known as blood pressure. To withstand this pressure, elastic fibers interspersed along the artery walls allow the arteries to expand and recoil. Abnormally high blood pressure, however, will cause these muscles to thicken as a result of tears in the damaged artery walls trapping particles that aggregate as plaque. Progressive build-up of plaque ultimately leads to a narrowing of the arteries, subsequently diminishing blood flow to the heart and other body organs. This cascade of events triggered by high blood pressure illustrates why hypertension is one of the most important risk factors for cardiovascular disease. Affecting 1 in every 3 adults in the United States alone, hypertension substantially raises the risk for heart disease in an affected individual who, most likely, does not show any signs or symptoms. In addition to the risks associated with this “silent killer,” comorbidities such as obesity, diabetes, and high cholesterol can drastically worsen health outcomes in hypertensive patients. Given the high prevalence and severe consequences of hypertension if undetected, researching this particular topic will increase our understanding of the causes of hypertension by identifying and narrowing down lead candidates for pot...
Ammonium nitrate was a key ingredient in a bomb that killed hundreds of people. It is an odorless crystal salt that can be either white or grey. It is created by a combination of ammonia and nitric acid. (ammonium Nitrate fact sheet). The primary uses for this chemical are fertilizers and cold packs, as well as military explosives (Mathews J, 2014). Not only is it an oxidizer but under enough heat and pressure, it can explode (ammonium Nitrate fact sheet). This explosive property leads to it being labeled a hazardous chemical in toxicology reports. In the past it has been a part of terrorism attacks such as the Oklahoma City bombing and accidental explosions in fertilizer factories. The Oklahoma City bombing is known as
Coronary artery disease (CAD) is the number one killer in America, affecting more than 13 million people. CAD occurs when a fatty substance called plaque builds up in the coronary arteries. These arteries disperse oxygen-ric...
Oxygen is widely used in both chronic and acute cases, in emergency medicine, at hospital or by emergency medical services (Nicholson, 2004 ). Just like any other form of medication oxygen is a drug that if used incorrectly could cause potential harm, even death (Luettel, 2010 ). Oxygen is admitted to the patient with chest pain for two main rationales. The first is by increasing arterial oxygen tension, which in opposing causes a decrease to the acute ischemic injury, and thus over time the entire infarct area (Moradk...
Erucic acid worked and is still used today. Erucic is extracted from canola/rapeseed. It distracts one of the enzymes, preventing it from metabolizing the wrong fatty acid. In many eastern countries canola was found to prevent heart disease.
United States. National Center for Biotechnology Information. U.S. National Library of Medicine. High Blood Pressure. Ed. A.D.A.M. Editorial Board. U.S. National Library of Medicine, 23 June 2012. Web. 29 Nov. 2013.
The Solubility of Potassium Nitrate Aim To investigate how the solubility of Potassium Nitrate is affected by Temperature. Background Knowledge Potassium Nitrate (KNO3) is an ionic compound. The strong ionic bonds hold the compound in an ionic lattice which gives KNO3 its crystalline structure. These ionic bonds also have other properties which will affect my investigation, I must be aware of these properties for greater accuracy in my method.