<unk> s reduce the activity of the renin–angiotensin–aldosterone system (RAAS) as the primary etiologic (causal) event in the development of hypertension in people with diabetes mellitus, as part of the insulin-resistance syndrome or as a manifestation of renal disease. Renin–angiotensin–aldosterone system Renin–angiotensin–aldosterone system The renin–angiotensin–aldosterone system is a major blood pressure regulating mechanism. Markers of electrolyte and water imbalance in the body such as hypotension, low distal tubule sodium concentration, decreased blood volume and high sympathetic tone trigger the release of the enzyme renin from the cells of juxtaglomerular apparatus in the kidney. Renin activates a circulating liver derived prohormone angiotensinogen by proteolytic cleavage of all but its first ten amino acid residues known as angiotensin I.<unk>  (angiotensin converting enzyme) then removes a further two residues, converting angiotensin I into angiotensin II.<unk>  is found in the pulmonary circulation and in the endothelium of many blood vessels. The system increases blood pressure by increasing the amount of salt and water the body retains, although angiotensin is also very good at causing the blood vessels to tighten (a potent vasoconstrictor). Effects<unk> s block the conversion of angiotensin I (ATI) to angiotensin II (ATII). They thereby lower arteriolar resistance and increase venous capacity; decrease cardiac output, cardiac index, stroke work, and volume; lower resistance in blood vessels in the kidneys; and lead to increased natriuresis (excretion of sodium in the urine). Renin increases in concentration in the blood as a result of negative feedback of conversion of ATI to ATII. ATI increases for the same reason; ATII and aldosterone decrease. Bradykinin increases because of less inactivation by<unk> . Under normal conditions, angiotensin II has these effects: * Vasoconstriction (narrowing of blood vessels) and vascular smooth muscle hypertrophy (enlargement) induced by ATII may lead to increased blood pressure and hypertension. Further, constriction of the efferent arterioles of the kidney leads to increased perfusion pressure in the glomeruli. * It contributes to ventricular remodeling and ventricular hypertrophy of the heart through stimulation of the proto-oncogenes c-fos, c-jun, c-myc, transforming growth factor beta (TGF-B), through fibrogenesis and apoptosis (programmed cell death). * Stimulation by ATII of the adrenal cortex to release aldosterone, a hormone that acts on kidney tubules, causes sodium and chloride ions retention and potassium excretion. Sodium is a "water-holding" ion, so water is also retained, which leads to increased blood volume, hence an increase in blood pressure. * Stimulation of the posterior pituitary to release vasopressin (antidiuretic hormone, ADH) also acts on the kidneys to increase water retention. If ADH production is excessive in heart failure, Na+ level in the plasma may fall (hyponatremia), and this is a sign of increased risk of death in heart failure patients. * A decrease renal protein kinase C During the course of<unk>  use, the production of ATII is decreased, which prevents aldosterone release from the adrenal cortex. This allows the kidney to excrete sodium ions along with obligate water, and retain potassium ions. This decreases blood volume, leading to decreased blood pressure. Epidemiological and clinical studies have shown<unk> s reduce the progress of diabetic nephropathy independently from their blood pressure-lowering effect. This action of<unk> s is used in the prevention of diabetic renal failure.<unk> s have been shown to be effective for indications other than hypertension even in patients with normal blood pressure. The use of a maximum dose of<unk> s in such patients (including for prevention of diabetic nephropathy, congestive heart failure, and prophylaxis of cardiovascular events) is justified, because it improves clinical outcomes independently of the blood pressure-lowering effect of<unk> s. Such therapy, of course, requires careful and gradual titration of the dose to prevent the effects of rapidly decreasing blood pressure (dizziness, fainting, etc.).<unk> s have also been shown to cause a central enhancement of parasympathetic nervous system activity in healthy volunteers and patients with heart failure. This action may reduce the prevalence of malignant cardiac arrhythmias, and the reduction in sudden death reported in large clinical trials.<unk> s also reduce plasma norepinephrine levels, and its resulting vasoconstriction effects, in heart failure patients, thus breaking the vicious circles of sympathetic and renin angiotensin system activation, which sustains the downward spiral in cardiac function in congestive heart failure The<unk>  enalapril has also been shown to reduce cardiac cachexia in patients with chronic heart failure. Cachexia is a poor prognostic sign in patients with chronic heart failure.<unk> s are under early investigation for the treatment of frailty and muscle wasting (sarcopenia) in elderly patients without heart failure.
ACE inhibitor
Calcium channel blocker
Beta blocker
Angiotensin II receptor blocker
Lipase inhibitors
Antiplatelet drug
SGLT2 inhibitor
Potassium binder