Abstract
The literature defines hypertension as a medical condition experienced when the systolic blood pressure (BP) is equal or greater than 140 mm Hg or when the diastolic blood pressure is equal or greater than 90 mm Hg. Additionally, it offers a description of systematic, cellular, as well as molecular causes of hypertension. High blood pressure within the arteries is referred to as systemic hypertension (SH). The primary role of the systemic arteries is the transportation of oxygenated blood from the heart to the tissues of the body. The constriction of the arterioles (small arteries) is responsible for the high blood pressure experienced in the systemic system. The major cause of primary systemic hypertension (PSH) is yet to be known. However, systemic hypertension can also be caused by an underlying disease or condition. Pulmonary arterial hypertension (PAH) or cellular causes of hypertension are caused by several factors that are interlinked. Thrombosis, vasoconstriction, as well as remodelled walls of the pulmonary vessels, contribute to the increase in resistance within the pulmonary system. The molecular mechanism behind pulmonary arterial hypertension is not yet known. However, there is a belief that a dysfunction in the endothelium can result in the decrease of certain vasodilators. The paper offers current as well as future treatments of hypertension. Plans for treating hypertension are individualized to best manage the definite cause as well as the age of a patient, severity of the condition, as well as medical history. Finally, the paper shows that significant progress has been noted in the treatment of hypertension. Nonetheless, there are some people experiencing treatment resistant hypertension, as such, there should be a novel treatment to help such people.
Key words: Hypertension, systolic, diastolic,
Introduction
The paper discusses the definition of hypertension, gives various causes of hypertension, for instance, cellular, as well as systematic causes. Besides, the script examines the current as well as future treatment of hypertension. Hypertension can be described as a medical condition experienced when the systolic blood pressure (BP) is equal or greater than 140 mm Hg or when the diastolic blood pressure is equal or greater than 90 mm Hg (Aiyagari & Gorelick, 2011). The systolic blood pressure denotes pressure within the arteries produced when the ventricles of the heart contract and the diastolic blood pressure designates the pressure within the arteries experienced when the ventricles relax and are filled with blood (Aiyagari & Gorelick, 2011). A 120 mm Hg or less systolic blood pressure, as well as an 80 mm Hg or less diastolic blood pressure, is considered normal BP. Hypertension can be grouped into three categories. Essential hypertension is experienced when the disease has an unknown cause. Secondary hypertension occurs when the condition is because of a disease process or other medical conditions. If the numerator or the systolic pressure is elevated, it is referred as isolated systolic blood pressure (hypertension), a condition most of the time common among older adults.
Most individuals are not informed that they suffer high blood pressure due to common symptoms’ inadequacy until serious complications emerge. In rare instances, some individuals suffering from hypertension can experience nosebleeds or headaches. In spite of common symptoms' inadequacy, uncontrolled elevated blood pressure destroys the heart or blood vessels as well as kidney. This can result from excessive as well as continuing blood pressure on arteries. Untreated elevated blood pressure can lead to dangerous and fatal aneurysms or abnormal arteries' ballooning, which may rupture. An elevated blood pressure may result in vision changes as well as blindness because of arteries bursting in one's eyes.
Causes of Hypertension
High blood pressure has many causes. Hypertension is associated with old age. Additionally, the condition can result from other health conditions, for example, chronic kidney illness as well as thyroid disease. Besides, hypertension can be due to side effects of some medications, for instance, oral contraceptives and hormone drugs. Heredity, as well as obesity, plays a significant contribution in causing hypertension. The disease most of the times is referred as a silent killer since it lacks symptoms until severe health complications emerge. Whenever symptoms of hypertension manifest, they may vary between people based on such characteristics as the age, medical history, blood pressure level, underlying cause, health complications, as well as overall health status.
Blood pressure denotes the pressure against the arteries’ walls as the blood flows via a circulatory system. More often than not, the blood pressure can fall or rise due to many situations or circumstances. For instance, blood pressure (BP) can increase due to strenuous activities to guarantee that body’s cells get extra oxygen-rich or sufficient blood. Besides, the pressure of blood can increase due to stressful circumstances. On the contrary, the pressure of blood can decrease as an individual sleeps or relaxes. Normally, the effects of BP that remains high or elevated for too long can lead to severe health complications (Mensah, 2010).
Systematic Causes of Hypertension
High blood pressure within the arteries is referred to as systemic hypertension (SH). The primary role of the systemic arteries is the transportation of oxygenated blood from the heart to the tissues of the body. The lungs are the only organ that the systemic arteries do not supply with blood. The constriction of the arterioles (small arteries) is responsible for the high blood pressure experienced in the systemic system. The peripheral resistance is increased by the constriction, which increases the workload of the heart. The increasing peripheral resistance raises the pressure in the arteries (Klabunde, 2012).
The major cause of primary systemic hypertension (PSH) is yet to be known. However, systemic hypertension can also be caused by an underlying disease or condition. This type of systemic hypertension is referred to as secondary systemic hypertension (SSH). For instance, when an aorta narrows, it can lead to systemic hypertension. Some of the possible causes of systemic hypertension include kidney disease as well as certain disorders of the endocrine system (Klabunde, 2012). Some of the common causes of angina pectoris in individuals with systemic hypertension include endothelial dysfunction and capillary rarefactions. These can also result in systemic hypertensive disorders. Moreover, microvascular angina may also be caused by oestrogen hormone deficiency. This often occurs in women in their post-menopausal period.
Cellular Causes of Hypertension
Pulmonary arterial hypertension (PAH) is caused by several factors that are interlinked. Thrombosis, vasoconstriction, as well as remodelled walls of the pulmonary vessels, contribute to the increase in resistance within the pulmonary system (Cox, 1991). Remodelling of the pulmonary vascular is a process that involves nearly all layers of the walls of the vessel. The process is complicated by the heterogeneity of the cells that lie in each compartment of the walls of the pulmonary artery. All cell types including smooth muscles, fibroblasts, and the endothelial play a crucial role in Pulmonary Arterial Hypertension (PAH). It is believed that constriction of the pulmonary vessels is an early process in the development of the hypertensive process. Abnormal expression or functioning of the potassium channels has been linked to excessive vasoconstriction. Additionally, a significant relationship exists between excessive vasoconstriction of the pulmonary vessels to endothelial dysfunction (Cox, 1991). Endothelial dysfunction impairs production of vasoconstrictors. These vasoconstrictors include prostacyclin and nitric oxide. The expression of endothelin (ET)-1 is also affected. The abnormalities have the potential to increase the vascular tone, promote the remodelling of the vascular, walls as well as acting as pharmacological targets.
The most common characteristic of the vascular endothelium of the Pulmonary Arterial Hypertension (PAH) is the imbalance in metabolites that are vaso-active. In the pulmonary arteries, there is a significant up-regulation of vaso-constrictive agents. These vaso-constrictive agents include endothelin-1 and thromboxane (Cox, 1991). However, the level of the vasodilators significantly reduces. These vasodilators include nitric oxide, prostacyclin, as well as guanosine monophosphate. The mechanisms that lead to the diminishing of upstream catalysts of the proteins, nitric oxide (NO) synthase, and prostacyclin synthase is still unclear.
Molecular Causes of Hypertension
The molecular mechanism behind pulmonary arterial hypertension is not yet known. However, there is a belief that a dysfunction in the endothelium can result in the decrease of certain vasodilators. The decrease of these vasodilators leads to constriction of the pulmonary arteries. Such vasodilators include the prostacyclin and nitric oxide. Moreover, stimulation of the production of vasoconstrictors such as VEGF and thromboxane also occurs.
Vasoactive Intestinal Peptide, Nitric Oxide and Prostacyclin
Prostacyclin commonly referred to as prostaglandin I2 is a crucial vasodilator of the pulmonary. It acts by activating the pathways that are dependent on the cyclic adenosine monophosphate (cAMP). Additionally, prostaglandin I2 restricts the growth of smooth muscle cells of the vascular system. It also leads to decreased platelets aggregation. In patients suffering from PAH, there is a drop in the synthesis of prostacyclin in the endothelial cells. When urinary metabolites are analysed, a significant decrease in the level of 6- keto prostaglandin F1 alpha is noted. Besides, there is often a decrease in the expression of prostacyclin synthase within the pulmonary cells of patients with PAH. On receiving prostaglandin therapy, these patients tremendously improve.
Demonstration in the reduction of nitric oxide further supports impaired vasodilation that is derived from the endothelium. A therapeutic strategy in pulmonary arterial hypertension aims at increasing vasodilation. This type of vasodilation often depends on inhibited breakdown of cyclic guanosine monophosphate (CGMP) (Das, 2011). The breakdown is catalyzed by phosphodiesterase type-5. The use of sildenafil has been regarded as effective and safe when given in chronic doses.
Vasoactive intestinal peptide (VIP) is a potent pulmonary as well as a systemic vasodilator. It is a neuropeptide that functions primarily as a neurotransmitter. Additionally, it inhibits the aggregation of platelets as well as the growth of smooth muscle of the vascular system. VPAC-1 and 2 regulate its actions. These are the subtypes of a receptor. The expression of these receptor subtypes occurs in the lung vasculature. They are often coupled with adenylate cyclase. The activation of the cyclic guanosine and cAMP occurs when the VPAC receptors are stimulated (Das, 2011). In idiopathic pulmonary arterial hypertensive patients, a decrease in VIP immunoreactivity, as well as serum concentration, is often noted. The deficiency in VIP is reflected by elevation in the binding activity of specific receptors. The increased expression of the VIP receptors is also linked to the proliferation of smooth muscle cells.
Endothelin ET-1
Endothelin ET-1 acts on endothelin receptor A (Eta) that is found in the smooth muscle cells of the pulmonary arteries. Its action leads to increased intracellular calcium. Additionally, the action of endothelin ET-1 enhances the continuous activation of an enzyme known as protein kinase C (pk C). The smooth muscles of the pulmonary artery are activated mitogenically through the action of endothelin receptor B or the ETA. This depends on the location of the cells anatomically. For example, the mitogenesis of particular cells that are derived from the primary pulmonary artery is mediated by the ETA. In contrast, both subtypes of the receptors usually contribute. Strong evidence exists on the contribution of ET-1 derived from the endothelium in the imbalance of either the vasodilators or the vasoconstrictors in patients with pulmonary arterial hypertension.
The levels of circulating as well as the lung ET-1 has been found to increase in patients and animals with pulmonary hypertension from different causes. From the observations, it can be deduced that there is a significant relationship between ET-1 and the vasoactive component of pulmonary hypertension (Das, 2011). Additionally, the ET-1 is linked to the abnormalities observed in the remodelling of the pulmonary vascular. ET antagonistic therapy has also supported the relationship between ET-1 and pulmonary arterial hypertensive (PAH).
Potassium Channels
Understanding the mechanisms behind hypoxic pulmonary vasoconstriction (HPV) is crucial to pulmonary arterial hypertension. However, PAH involves abnormalities and proliferation of cell death. When some potassium channels, which are voltage-gated (Kv), are inhibited, hypoxic pulmonary vasoconstriction occurs. This inhibition occurs in the smooth muscles of the pulmonary arteries. In individuals with the pulmonary artery hypertension, there is down-regulation of the Kv 1.5. However, both Kv1.5 and KV2.1 are often down regulated in rats experiencing pulmonary hypertension induced by hypoxic conditions.
Through deoxyribonucleic acid (DNA) microarray studies, it has been shown that down regulation of Kv channels have genes in pulmonary arterial hypertensive lungs. The depolarization of smooth muscle cells of the pulmonary arteries is caused by the selectivity in the loss of Kv channels. These also lead to increased intracellular calcium, cell proliferation, as well as vasoconstriction. It is yet to be known whether the abnormalities in the Kv channels are acquired or genetically determined. However, there is adequate evidence supporting the use of aminorex and dexfenfluramine to inhibit the Kv 1.5 as well Kv 2.1 channels. Drugs such as sildenafil and dichloroacetate have been proven to enhance the function as well as expression of the potassium channels (Kv). The cyclic guanosine monophosphate mediates on the effects of nitric oxide. This causes vasodilation through the activation of protein kinase G. The primary role of the protein kinase G is to activate as well as phosphorylate the BKca channels (Das, 2011). This is one of the mechanisms used in lowering the level of systolic calcium. Understanding these pathways is essential for any intervention regarding the pulmonary arterial hypertension.
Current as well as Future treatments of Hypertension
Plans for treating hypertension are individualized to best manage the definite cause as well as the age of a patient, severity of the condition, as well as medical history. Hypertension or high blood pressure can be treatable and in many instances, prompt as well as continuous treatment can lead to a normal blood pressure or minimize the possibility of severe health complications. Hypertension treatment starts with prevention. Such a plan involves keeping a good or healthy weight, eating a balanced diet, regular exercise, not smoking, as well as not consuming excessive alcohol. Such preventive measures are recommended as measures of treatment. It is a challenge for many persons suffering from hypertension to manage the condition exclusively by life style measures. For such individuals, oral medications, called anti-hypertensive medications can be recommended or prescribed. Drugs can be utilized exclusively or with other drugs (Messerli, 2011).
Examples of anti-hypertensive drugs are diuretics or water pills that lower pressure of blood by flushing excess salt as well as fluid from the circulatory system through the kidneys. The blood pressure is lowered by ACE inhibitors by stopping the body system from secreting a hormone referred as angiotensin II that helps in the narrowing as well as tightening of blood vessels. The receptor blockers of the hormone restrict narrowing of the blood vessels due to actions of angiotensin. Additionally, the beta blockers assist in controlling the rate of heart beats and maintains it at a slower pace as well as less forcefully (Neutel & SpringerLink, 2011). Calcium tubule blockers prevent calcium from infiltrating into cells of blood vessels and the heart leading to walls of blood vessels relaxing. Alpha-blockers lower impulses of the nerve, which tighten vessels of blood. Vasodilators widen as well as relax the walls of blood vessels. The inhibitors of nervous system function within the brain to accelerate messages to vessels to widen as well as relax such blood tubes.
Traditionally, there are five categories of medications utilized to treat hypertension. These include calcium-channel blockers, thiazide diuretics, alpha-blockers, angiotensin-converting inhibitors, as well as beta-blockers (Nissenson, Berns, & Lerma, 2009). Because of many drugs exists to treat hypertension, combination treatment can be an option to manage the condition. The combination of medications is used and has significant implications as well as prescribing expenses. The recommended combinations are used because they complement one another pharmacologically, for instance, thiazides and ACE inhibitors (Weir, 2010).
Fixed-dose combination treatment was not recommended previously due to the inflexibility of higher expenses as well as dosing in comparison to individual ingredients. Nonetheless, there are formulations of fixed-dose combination in use. A combination of valsartan, as well as amlodipine, referred as exforge represents a recently launched or released combination therapy. Ang II and calcium-channel blockers (CCB) make a combination claimed to lower the peripheral oedema risk, which can be caused by CCB (Frishman & Sica, 2011). The hypertension treatment can also involve managing the underlying causes, for example, obesity, kidney, as well as thyroid diseases. If the cause of hypertension is medication or drug, then an adjustment of a dosage or different drug can be appropriate.
Future Hypertension Treatment
The present activities by international firms seem to be concentrated on coming up with a novel combination pills, for example, polypills and fixed-dose combination. The interest or enthusiasm of developing novel categories of antihypertensive drugs is high. Exforge HCT, as well as tribenzor, represent novel combination therapies, which combine three antihypertensive drugs that got the approval of FDA (Phillips, 2015). Tribenzor has olmesartan, hydrochlorothiazide, as well as amlodipine, got approval under the condition that the therapy cannot be employed as the first treatment. Exforge HCT contains valsartan, amlodipine, as well as hydrochlorothiazide and represents an oral drug available in strengths of different ranges.
LCZ696 represents few novel categories of treatment being investigated for treating heart failure as well as hypertension. The drug combines some active moieties of two drugs. LCZ696 is in the second stage of trial and is promising since it had a significant average reduction of diastolic as well as the systolic pressure of blood in comparison of valsartan acting alone (Antel, Hesselink, & Schermuly, 2010).
Another new as well as interesting technique of treating hypertension in early development stage is the employment of vaccines. The initial stage two of ang 2 vaccine among hypertension patients had a promising outcome of an average reduction of systolic BP by 9 mm Hg and diastolic BP by 4 mm Hg respectively.
Carotid stimulation treatment is another promising alternative for treating hypertension. Arterial baroreceptors stimulation found within the aortic arch as well as carotid sinuses, through increased vascular distension leads to a lower rate of sympathetic activities. For example, it reduces activity in the vasculature, kidneys, heart, lowers production of arginine vasopressin by posterior pituitary, as well as intensifies parasympathetic tone within the heart. Carotid stimulation leads to reductions in stroke volume, vascular resistance, heart rate, and blood pressure (Antel, Hesselink, & Schermuly, 2010). The baroreflex modulation to manage hypertension was at first doubted because baroreflex must be reset to address the increase of blood pressure. However, research has demonstrated that baroreflex modulation offers a way of managing severe hypertension. After trials and research, such a device exists and is referred as Rheos Baroreflex stimulation or activation treatment system. It consists of a gadget, which is implanted in the body of a patient and connected to carotid sinuses. Baroreflex modulation is achieved by externally setting the signalling frequency of the device.
Conclusion
In summary, the paper has offered a definition of hypertension. It covers different causes of hypertension such as systematic, cellular, as well as molecular causes of high blood pressure. Besides, the paper shows that significant progress has been noted in the treatment of hypertension. Nonetheless, there are some people experiencing treatment resistant hypertension, as such, there should be a novel treatment to help such people.
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