A Relationship Between Some Neurotransmitter Controlling Enzymes And Essential Hypertension

Hypertension, also known as high blood pressure, has become a major risk factor for several types of heart disease across the globe. In the United States alone, nearly 70 million adults have been diagnosed with this condition [1]. Hypertension is a condition in which arterial walls experience extreme force from blood flowing through; long-term force against artery walls will lead to more serious health problems such as stroke, renal failure, and other cardiovascular diseases [2]. If the proper steps to treat hypertension are not taken, patients have a high risk of developing atherosclerosis, a condition that causes arteries to harden significantly. Smoking, obesity, lack of physical activity, high alcohol consumption, and high sodium intake are factors that may cause an individual to be diagnosed with hypertension [3] Detection of hypertension is crucial in order to reduce the incidence of death by cardiovascular disease [1].

When substances like Acetylcholine (Ach) and norepinephrine which are small- molecular neurotransmitters are released into the body they bind to receptors on tissue or neurons through our ANS and PNS system. Ach is released by many PNS neurons and some CNS neurons. In the PNS Ach is an excitatory neurotransmitter at some synapses, such as the neuromuscular junction where it binds to ionotropic receptors which open cation channels. Ach can also be an inhibitory neurotransmitter at other synapses, where it binds to metabotropic receptors while opening potassium channels. The enzyme acetylcholinesterase (AchE) inactivates Ach by splitting into acetate and choline fragments. Norepinephrine (NE) is a biogenic amine; most biogenic amines may cause

Cholinesterases are a group of enzymes present in mammals which breakdown certain neurotransmitters by hydrolyzing the ester bonds within a molecule (Rang & Dale, 2007). There are two major types of enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Though similar in structure, they differ in distribution, function and substrate specificity.

- Lilly et al, Pathophysiology of Heart Disease, 5th Ed., Lippincott Williams & Wilkins, 2011.

The second neurotransmitter family includes amino acids, compounds that contain both an amino group (NH2) and a carboxylic acid group (COOH) and which are also the building blocks of peptides and proteins. The amino acids known to serve as neurotransmitters are glycine, glutamic and aspartic acids, all present in all proteins, and gamma-amino butyric acid (GABA), produced only in brain neurons. Glutamic acid and GABA are the most abundant neurotransmitters within the central nervous system, particularly in the cerebral cortex; glutamic acid tends to be excitatory and GABA inhibitory. Aspartic acid and glycine subserve these functions in the spinal cord (Cooper, Bloom, and Roth 1996).

Nitric oxide (NO) acts as a messenger molecule produced by the NO synthase (NOS) isoforms neuronal NOS (nNOS, or NOS1), inducible NOS (iNOS, or NOS2), and endothelial NOS (eNOS, or NOS3). NO has been involved in relaxing smooth muscle, inhibiting smooth muscle cell migration and proliferation, and decreasing platelet adherence and aggregation. NO also inhibits vascular inflammation [1].

My mother, Nanci, my uncle, Mike, and my aunt Kim have all been diagnosed with hypertension. Hypertension, also known as high blood pressure is the most common cardiovascular disease and leads to over 326,000 deaths in the United States every year (Adams & Urban, 2013). Hypertension is consistent increased systemic arterial blood pressure, and can be divided into two categories, primary and secondary. Primary hypertension has no identifiable cause, and according to Adams and Urban is responsible for almost 90% of all cases of diagnosed hypertension (Adams & Urban, 2013). Secondary hypertension on the other hand is related to an underlying disease process or condition, such as hyperthyroidism or the use of corticosteroids. Hypertension can systemic issue, which means that the blood pressure of the entire body is affected, or it can be a localized issue where only certain tissues are affected, such as the liver. Hypertension is usually an asymptomatic issue, however, when symptoms do appear, they have been caused by the long-term existence of the disorder, over years or decades. Over time, the elevation of the blood pressure begins to wear on the arteries and the organs of

There are many different neurotransmitters that can be described in this unit but I will only be discussing four. The first Neurotransmitter which is located near the cortex, spinal cord, and target organs is activated by the parasympathetic nervous system which is called Acetylcholine (ACh). It was the first neurotransmitter discovered. This neurotransmitter was released from motor neurons to muscle fibers to make them bond. It affects learning and memory in the brain. A behavior that it can cause is Alzheimer 's disease. The disease involves decay of acetylcholine neurons in the brain. There is not yet a treatment for the disease but drugs with acetylcholine in it are able to be used to treat the drug.

Impairment of endothelium-dependent vasodilation changes the well-regulated mechanism connecting tissue metabolic needs and regional blood flow, whereas the loss of the anti-adhesive and anti-aggregative properties of the endothelium favors the accumulation of leukocytes and platelets in the microcirculation. This leads to the impaired microvascular perfusion and organ functions. Villa and co-workers provided the first observation implying peroxynitrite as a mediator of endothelial dysfunction by peroxynitrite infusion in isolated perfused hearts resulting in severe impairment of endothelial-dependant relaxation in coronary vessels [12]. In conclusion, peroxynitrite could also trigger endothelial dysfunction during shock by an indirect way involving the activation of PARP, as shown in endothelial cells in vitro (Szabó et al., 1997), as well as in vivo models of shock in which endothelial dysfunction could be corrected by pharmacological PARP inhibitors [60,70] or its genetic deletion

Many of the vaso-protective function of endothelium is provide by the Nitric Oxide(NO)20.Endothelium damaged by turbulent or non-laminar blood causes decreased production of NO.Such kind of blood flow also stimulates endothelial cells to produce adhesion molecules, which recruit and bind inflammatory cells. Hypercholesterolemia seems to inactivate the normal function of NO. The net effect is endothelial binding of monocytes and T cells, migration of these cells to the subendothelial space, and initiation of a local vascular inflammatory response. Lipids in the blood, particularly low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), also bind to endothelial cells. 18Firstly LDL is transported across the healthy intima and become trapped in intima of a vessel wall.It undergoes oxidative modification and then oxidized LDL(OxLDL) is formed5.OxLDL is mighty inducer of inflammatory molecules.It adds up to the inflamotory signaling by endothelium that activates chemotactic substances, growth factors that attracts monocytes to vessel wall21Eventually OxLDL transforms monocytes into macrophages which makes the Forms cells, which are the hallmark of atherosclerosis. Oxidized LDL impair the signal transduction between endothelial cell surface receptors and NO production, inhibit NO synthase activity and inactivates NO realese from endothelial cells.22.Once the endothelium is impaired, oxidized LDL is stored in vascular endothelium and by the process of series of mechanism, foam cells are formed and then eventually fatty plaque that occludes the vessel along with the decreased amount of NO which decreases the ability of the vessel to dilate. As the plaque grows arterial wall narrowing and thickening occurs5. This plaque and narrowing of vessel results in decreased blood flow

Hypertension is widely considered to be one of the most important risk factors of cardiovascular diseases (angina, arrhythmia, etc.). It is the second leading disease that causes mortality in the world. Hypertension is the condition when there is an increase in the force of blood on the walls of vessels. It can also be defined as an arterial blood pressure that is raised above 140/90 mm Hg (systolic/ diastolic BP). Hypertension can be classified into Secondary hypertension and Essential hypertension. When specific cause is evident but heredity, and various physiological parameters play a role in increasing blood pressure is known as Essential Hypertension. Secondary Hypertension is one where the cause is known. According to WHO guidelines between 2006 and 2015, deaths due to cardiovascular diseases are expected to increase by 17% while the deaths from infectious diseases, nutritional deficiencies, maternal and prenatal conditions are projected to decline by 3%. The main causes of hypertension includes the age ,hereditary, gender, extra weight, alcohol consumption, stress life, lazy life etc.

Hypertension is a growing health problem with over one billion estimated cases worldwide. (Kumari, Kaur, & Kaur 2015) Kumari et al (2015)

Numerous previous studies have shown that nitric oxide (NO) has been considered as a significant biological regulator which is beneficial for nervous system, cardiovascular system, lungs, gastrointestinal tract, renal system, and immune system. Previous studies have shown it regulates blood flow, muscle contractility, myocyte differentiation, glucose and calcium homeostasis, and mitochondrial respiration and biogenesis. [1]

Approximately one in every three adult’s ages 20 years old and older are diagnosed with high blood pressure or hypertension. Hypertension affects 78 million people in the United States and is equally prevalent in both men and woman (Crabtree et al., 2013). Hypertension is a major risk factor for cardiovascular disease (Hajjar & Kotchen, 2003). It can lead to stroke, myocardial infarction, renal failure, heart failure, neurological issues, and death if not detected early and not treated properly (James, Oparil, Carter, & et al., 2014). Approximately 9.4 million deaths in 2010 were attributed to high blood pressure (Angell, De Cock, & Frieden, 2015). About 54% of strokes, 47% of coronary heart disease, and 25 % of other cardiovascular diseases are attributed to high blood pressure (Arima, Barzi, & Chalmers, 2011).

The two major types of hypertension are primary and secondary. Primary hypertension accounts for more than 90% of all cases and has no known cause, although it is hypothesized that genetic factors, hormonal changes, and the altercations in sympathetic tone all may play a role in its development. Secondary hypertension develops as a consequence of an underlying disease or condition. The prevention and treatment of hypertension is a major public health issue. When blood pressure is controlled, cardiovascular, renal disease, and stroke may be prevented. The JCN, reported more than 122 million individuals in American are overweight or obese, consume large amounts of dietary sodium and alcohol, and do not eat adequate amounts of fruits and vegetables; less than 20% exercise regularly. Both modifiable and non-modifiable factors play a role in the development of hypertension