INTRODUCTION:- HISTORICAL BACKGROUND OF ANTIHYPERTENSIVE THERAPY Antihypertensive therapy with the

There are many methods of treatment for hypertension. This includes exercise, a healthy diet, quitting smoking, and medications. Some medications that might be prescribed to a hypertension patient are thiazide diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and renin inhibitors. Thiazide diuretics, also known as water pills, help improve the kidneys. They eliminate the sodium (salt) and excess water which reduces the blood volume. Thiazide diuretics are most commonly the first drug that is prescribed to a hypertension patient. These types of drugs include hydrochlorothiazide (Microzide), chlorthalidone, and many others. Beta

Beta blockers, also known as beta-adrenergic blocking agents, are medications that reduce your blood pressure. Beta blockers work by blocking the effects of the hormone epinephrine, also known as adrenaline. When you take beta blockers, your heart beats more slowly and with less force, thereby reducing blood pressure. Beta blockers also help blood vessels open up to improve blood flow. Examples of Beta Blocker include; Metoprolol (Lopressor), Atenolol (Tenormin) and Carvedilol (Coreg).

Aldosterone is the mineralocorticoid steroid which is release from the adrenal gland, situated superior to the kidney. Aldosterone play a major role for the retention of water and sodium in the nephrone (10) in the patient with congestive heart failure, cirrhosis, and nephrotic syndrome (25). The level of the Aldosterone will increase in the patient of heart failure when angiotensin I receptors is activated by Angiotensin II leading to fluid overload (10).

The mechanism of action of the two types of drugs are very similar, but evidence has shown that the ARB is less effective at decreasing the mortality and morbidity rates (Burchum and Rosenthal, 2016).

While RAAS can be good for blood pressure maintenance there are some drawbacks. Angiotensin II can cause structural changes of the heart and blood vessels. It can be implicated hypertrophy and remodeling within the heart. Aldosterone also has adverse effects. Like angiotensin II, aldosterone can cause cardiac remodeling as well as a decreased reuptake of norepinephrine in the heart. This can increase the chances of dysrhythmias (Burchum 472). In a healthy heart these adverse effects would not be seen, but in a heart already in dysfunction, it can cause further complications. The mechanism of action several drugs is to control the outcome of this system.

Angiotensin II is an octapeptide which is associated with the cardiovascular system. It maintains blood pressure by vasoconstriction and stimulation of aldosterone secretion. Angiotensin II is synthesized through the renin-angiotensin system (RAS) which is known to be involved in systemic blood pressure control, including the regulation of cerebral blood flow (Mogi, Iwanami, & Horiuchi, 2012). Renin, a product of the juxtaglomerular cells of the kidney, is released into the circulation where it cleaves the angiotensinogen to form angiotensin I. Angiotensin I is cleaved by angiotensin-converting enzyme (ACE) to form the angiotensin II. Apart from the production of angiotensin II in plasma and peripheral organs such as kidney, adrenal gland,

ACEI causes hyponatremia by blocking the conversion of angiotensin I to angiotensin II in the peripheral circulation but not in the brain where angiotensin I gets converted to angiotensin II [16]. Angiotensin II is known to stimulate the release of ADH resulting in hyponatremia [18].

An angiotensin-converting-enzyme (ACE) inhibitors use in the management of hypertension and secondary prevention of stroke is supported by NICE guidelines, and is effective with a favourable side effect profile.

The explanation for presentation of this group is multifactorial including advanced stage of heart failure, old age, hypertension, diabetes mellitus, acute coronary syndrome, secondary to aggressive diuresis as supported by increased use of loop and potassium sparing diuretics and an intrinsic imbalance between the vasoconstrictive (epinephrine, angiotensin, endothelin) and vasodilatory hormones (natriuretic peptides, nitric oxide). 7

The kidneys play a part in the regulation of blood volume and blood pressure. The kidneys Juxtaglomerular cells are the primary site for renin storage and release, the renin responses to the body’s low and high blood pressure (Jenkins & Tortora, 2013). If the renin angiotensin aldosterone system (RAAS) is interrupted due to the formation of AVAs in the kidneys this could cause renal hypertension. This is the result from the narrowing and weakening of the kidneys arteries thus resulting in kidney failure because blood is not delivered to kidney tissue (Jenkins & Tortora,

Rate control is the older therapeutic strategy but it is still a primary therapy for AF. Beta-blockers and calcium channel blockers are both effective and well resistant therapies which can be used in a wide range of acute and long-term clinical conditions, as well as both contribute in controlling hypertension. It's investigated that oral beta-blockers are more favorable than calcium channel blockers for patients with ischemic heart disease, CHF and depressed left ventricular function. Digoxin is effective for controlling heart rate especially in sedentary elderly and concomitant CHF patients due to its effectiveness in improving ventricular function. Other potential advantages of rate control include less adverse drug effects and less hospitalization. However, it has some disadvantages including risk of toxicity, chronotropic incompetence and difficulties in achieving dose adjustments in patients with compromised renal function adding that it is not preferred in younger patients and those with a history of

Blood pressure is defined as the pressure of blood as it’s applied to the walls of blood vessels when the heart contracts. Blood pressure is important to homeostasis in the body because it helps maintain temperature and proper delivery of nutrients to the body. The kidneys depend on blood pressure for helping it filter blood and they also control one of the mechanisms for regulating blood pressure called long term blood pressure control. When the blood pressure is low, the kidneys release substance/enzyme called renin. Renin causes the production of a chemical known as angiotensin 2 through this cascade of reactions. Then, Angiotensin 2 causes constriction of blood vessels which means the lessening of the diameter in the blood vessels. When blood vessels are constricted the blood pressure rises. Another gland also helps out. This is called the adrenal gland. In this process, the adrenal cortex on the outside of the adrenal gland releases a substance called aldosterone in the presence of angiotensin 2. This substance increases sodium reabsorption in the body. This also increases water reabsorption. In addition, the reabsorbed water increases the blood volume which also increases the

Controlling blood glucose has been widely accepted as a method to reduce risk of atherosclerotic cardiovascular events and new-onset heart failure; although this observational relationship exists, no evidence from randomized controlled trials illustrates that improved glycemic control modifies risk. Many of the antihyperlipidemic agents, namely thiazolidinediones, dual peroxisome proliferator-activated receptor agonists, sulfonylureas, and insulin may cause adverse events such as increased plasma volume, exacerbation of heart failure, dysregulation of myocardial metabolism, and worsening of left ventricular function; therefore, a clinical concern exists with prescribing agents that may lead to morbidity and mortality.

These are the primary site at which another regulatory hormone, known as renin, is released [9]. Due to changes in the pressure within the afferent arteriole, renin release is either stimulated or inhibited. Speicalised cells called macula densa detect the level of NaCl in the distal tubule (see Fig.1.), when the level of NaCl is decreased, the sympathetic nervous system is stimulated causing beta-adrenoreceptors to stimulate the juxtaglomerular cells to release renin. When the level of NaCl is decreased, the juxtaglomerular cells are inhibited so do not release renin. Renin is crucial in the renin-angiotensin-aldosterone system (RAAS) as it acts upon angiotensin, allowing it to be cleaved by proteolytic enzymes forming angiotensin I. This is further cleaved by an angiotensin converting enzyme (ACE) to form angiotensin II. This substance stimulates thirst centres in the brain as well as stimulates the pituitary and adrenal glands to release AVP and another hormone called aldosterone [9]. Aldosterone is produced in the hypothalamus and released by the adrenal gland. It acts on the kidney by increasing the tubule permeability to water and sodium ions, causing more to be reabsorbed into the blood [2] and therefore decreasing urine output

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.