2.1 OXIDATIVE STRESS
The term oxidative stress is often used to imply a condition in which cells are exposed to excessive levels of either molecular oxygen or chemical derivatives of oxygen called reactive oxygen species; (Kojda et al., 1999). This occurs when molecules of oxygen are reduced to various subunits such as water, the production of superoxide anion radical, hydrogen peroxide and hydrogen radicals (Geller, D.A., et al. 1993). On the other hand ROS has different effects on individual blood vessels and also play a very important role on the physiological and pathological aspects of the vessels. The main ROS in blood vessels are superoxides. Super oxides are formed from the remains of reduced oxygen which is catalysed by two enzymes which are NADPH oxidase and xanthine oxidase (Taniyama et al., 2003). Superoxides are able to act on different cells but it can produce ROS by reacting with other substances, for e.g. superoxides can react with Nitric oxide to produce peroxynitrite which is potentially deleterious of ROS (Helmut, 1997). This happens by the use of superoxide dismutase enzyme, by the use of this enzyme a production of stable ROS is formed such as hydrogen peroxide (H2O2) which is then broken down into water (H2O) and oxygen (O2), this occurs in all types of vascular cells (Taniyama et al., 2003)
Figure 1: Formation of free radicals in biological systems (Vet med, 2014)
2.2 ROLE OF REACTIVE OXYGEN SPECIES
The major source of reactive oxygen species in both endothelial and vascular smooth muscle cells are membrane bound oxidases, which utilise NADH and NADPH as substrates (Kojda et al., 1999).
Impaired endothelium dependent vasorelaxation:
ROS plays a very important role in the endothelium dysfunction and ...
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... migration and proliferation of smooth muscle cells which are involved in the inflammatory lesions. These aid in further thickening the artery by slow dilation, this is called “remodelling”. Monocyte-derived macrophages and specific subtypes of T lymphocytes are mainly associated with the inflammatory response (Russell, 1997).
Normal endothelium permeability is mediated by nitric oxide. So an unbalance in this would lead to an increase in the endothelial permeability and thus leads to formation of atherosclerosis lesions. At the beginning fatty streaks are made of monocytes consisting of lipids and macrophages along with T-lymphocytes and this combines with the smooth muscle cells in later stages. This leads to a foam cell formation which is stimulated by macrophage stimulating factors, tumour necrosis factors and oxidised low density lipoprotein (Russell, 1997).
Margination and adhesion to the endothelium, in which accumulation of leukocytes occurs along the endothelial wall for adhesion. Afterward, these adhesions cause the separation of endothelial cells, allowing the leukocytes to extend and Transmigrate through the vessel walls. Followed by the response of chemical mediators(chemotaxis) that influence cell migration via an energy directed process which triggers the activation of Phagocytosis, in which monocytes, neutrophils, and tissue macrophages are activated to engulf and degrade cellular debris and
The gaseous free radical nitric oxide is an abundant intracellular messenger molecule that plays a central role in maintenance of health, and is heavily involved in signal transduction in various cells of the body [1]. This molecule acts as a mediator in the regulation of cardiac function as well as having an important role in regulating contractility of the heart and maintenance of vascular tone in the cardiovascular system. As one of the most significant individuals in our discovery of nitric oxide, Dr. Robert Furchgott pioneered our understanding of this molecule through his experiments on the vasorelaxant properties of acetylcholine and the subsequent proposal of the presence of the endothelium derived relaxing factor, which was later identified to be nitric oxide [7]. Given the observation that cardiovascular disorders are the number one cause of death in many nations around the world, research into the vasorelaxant properties seems particularly relevant in order to help combat rising rates of vascular hypertension and high blood pressure. In this paper, the properties of nitric oxide are discussed largely with respect to the cardiovascular system. This paper focuses on the synthesis and characteristics of nitric oxide, the mechanisms of action by which nitric oxide works and the regulation of nitric oxide in the body, and finally a short summary of Robert Furchgott’s contributions to the discovery of nitric oxide and its properties.
oxygen out of the blood and uses it in the body's cells. The cells use
Red blood cells deliver the oxygen to the muscles and organs of the body.
Atherosclerosis begins when the inner wall of the artery becomes damaged and cholesterol and fatty plaques begin to lodge in the arteries. Damage to the endothelial wall inside the artery can be caused by hypertension, hyperlipidemia, and hyperglycemia (“Subclinical Atherosclerosis..” 443). When this happens, the immune system responds by sending monocytes to the damaged area. The monocytes turn into macrophages; their job is to eat up the excess cholesterol and unblock the artery. The macrophages are unable to digest all of the cholesterol, and as a result turn in to foam cells. When many macrophages are turned into foam cells, plaque results, and protrudes into the arterial wall, restricting blood flow and raising blood pressure (“Atherosclerosis Growth Process.” 8). If the plaque becomes too large it may break, releasing plaque into the blood. This can cause a great reduction in blood flow or a clot, resulting in stroke or myocardial infarction (“Stroke Risk.” 3).
Coronary artery disease (CAD) is the most common type of multifactorial chronic heart disease. It is a consequence of plaque buildup in coronary arteries. The arterial blood vessels, which begin out smooth and elastic become narrow and rigid, curtailing blood flow resulting in deprived of oxygen and nutrients to the heart [1].
Besides regulating hemostasis, endothelial cells also possess important functions like permeability, regulation of vascular tone, immunity, leukocyte trafficking, inflammation and angiogenesis among others.[1][2][3].
High oxidative a stress is known to cause global cellular damage by creating reactive oxygen species (ROS) which causes damage to proteins, lipids and DNA (15, 82). Oxidative stress increases protein phosphorylation, causing changes to signaling pathways. For example, several phosphatases involved in cancer, apoptosis and aging are inactivated under conditions of high oxidative stress (26). ROS is a known contributor to several diseases including Alzheimer’s, Parkinson’s, Huntington’s, kidney disease, and T2DM (25, 27, 105). Known mediators of oxidative stress include transition metals and mitochondrial dysfunction (15, 27). In this project, I will be studying how cellular iron regulation causes an increase in oxidative stress, contributing to cellular damage and disease. Aconitase is an important mediator of oxidative stress, metabolism and iron regulation.
Coronary heart disease is defined by the hardening of the epicardial coronary arteries. The buildup of plaque in the arteries slowly narrows the coronary artery lumen. In order to better understand the physiology of the disease, it is important to first know the basic anatomy of the human heart. The aorta, located in the superior region of the heart, branches off into two main coronary blood vessels, otherwise known as arteries. The arteries are located on the left and right side of the heart and span its surface. They subsequently branch off into smaller arteries which supply oxygen-rich blood to the entire heart (Texas Heart Institute, 2013). Therefore, the narrowing of these arteries due to plaque buildup significantly impairs blood flow throughout the heart.
Another study proposed that CR slowed aging process by increasing resistance to hyperoxidation. As aging progressed in yeast and other animals, the presence of free radicals increased in the cells. Usually, the levels of the...
The circulatory system and respiratory system share a highly important relationship that is crucial to maintaining the life of an organism. In order for bodily processes to be performed, energy to be created, and homeostasis to be maintained, the exchange of oxygen from the external environment to the intracellular environment is performed by the relationship of these two systems. Starting at the heart, deoxygenated/carbon-dioxide (CO2)-rich blood is moved in through the superior and inferior vena cava into the right atrium, then into the right ventricle when the heart is relaxed. As the heart contracts, the deoxygenated blood is pumped through the pulmonary arteries to capillaries in the lungs. As the organism breathes and intakes oxygenated air, oxygen is exchanged with CO2 in the blood at the capillaries. As the organism breathes out, it expels the CO2 into the external environment. For the blood in the capillaries, it is then moved into pulmonary veins and make
To investigate the amount of oxygen foam (cm) produced by the enzyme catalase when it breaks down hydrogen peroxide in the animal (liver, milk, honey) and plant cells(potato, purple cabbage) into oxygen and water
of fatty substances on the inside wall of the arteries). It is not caused by
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...
The arteries supply blood rich in oxygen to the body, the veins direct deoxygenated blood from the capillaries back to the heart. These roles make up the circulatory function. Blood flow through these blood vessels can be disrupted resulting in peripheral vascular diseases. These diseases occur as a result of narrowing or blocking of the blood vessels. The risk factors of peripheral vascular diseases include diabetes, smoking, high level of cholesterol, overweight, high blood pressure etc. these risk factors result to aneurysms, Raynaud’s diseases, Buerger’s disease, renal artery disease etc. With this diseases, the peripheral vascular system should be assessed to enable nurses and other health personnel make good