Hypertension renin-angiotensin-aldosterone system

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels. 

Propranolol inhibits the stimulation of renin production by catecholamines (mediated by receptors). It is likely that propranolol s effect is due in part to depression of the renin-angiotensin-aldosterone system. Although most effective in patients with high plasma renin activity, propranolol also reduces blood pressure in hypertensive patients with normal or even low renin activity. Beta blockers might also act on peripheral presynaptic adrenoceptors to reduce sympathetic vasoconstrictor nerve activity. 

In most cases, elevated blood pressure is associated with an overall increase in resistance to flow of blood through arterioles, while cardiac output is usually normal. Meticulous investigation of autonomic nervous system function, baroreceptor reflexes, the renin-angiotensin-aldosterone system, and the kidney has failed to identify a primary abnormality as the cause of increased peripheral vascular resistance in essential hypertension. 

A test dose should be given to patients who are in cardiac failure (or who are already taking a diuretic for another reason, e.g. hypertension). Maintenance of blood pressure in such individuals may depend greatly on an activated renin-angiotensin-aldosterone system and a standard dose of an ACE inhibitor can cause a catastrophic fall in blood pressure. Except for captopril, most ACE inhibitors (including enalapril) are prodrugs, which are inactive for several hours after dosing. This has favoured the use of captopril... 

Insulin edema is a rare complication, more often seen in the earlier years of insulin therapy (SEDA-11, 364). It is mostly seen when dysregulated patients with progressive weight loss are treated with relatively high amounts of insulin. Reduced sodium excretion (88), sodium reabsorption, and water retention by a possible direct action of insulin on the kidney may be involved (89). The role of aldosterone or of inhibition of the renin-angiotensin-aldosterone system in insulin edema is unclear. Insulin edema is a specific adverse effect, but it can aggravate pulmonary edema, congestive heart failure, and hypertension. Treatment consists of reduction of the insulin dose, after which the edema resolves within 3 days. 

Other unusual conditions that suggest aldosterone excess or deficiency but are not connected to the renin-angiotensin-aldosterone system include Liddle s syndrome (pseudo hyper aldosteronism),which resembles primary aldosteronism clinically, but aldosterone production is low and hypertension is absent and Barttefs syndrome,which involves a prostaglandin-mediated renal potassium wasting and renal chloride handling defect, in which both aldosterone concentrations and renin activities are elevated. In renal tubular acidosis and pseudohypoaldosteronism, the clinical picture of hypoaldosteronism is seen concurrent with greater-than-normal concentrations of aldosterone. 

Captopril, l-[(2S)-3-mercapto-2-methyl-propionyl]-L-proline, the first orally active inhibitor of the angiotensin-converting enzyme (ACE) on the market. The positive effects of captopril and other ACE inhibitors like enalapril in hypertension and heart failure result primarily from suppression of the renin-angiotensin-aldosterone system. Captopril causes a fall in blood pressure in hypertensive patients [M. A. Ondetti et al.. Science 1977,196,441 ... 

Case DB, Atlas SA, Laragh JH, Sealey JE, Sullivan PA, McKinstry DN. Clinical experience with blockade of die renin-angiotensin-aldosterone system by an oral convertii -en me inhibitor (SQ14,225, captopril) in hypertensive patients. Prog CarSovasc Dis (1978) 21,195-206. 

Cardiovascular Paradoxical severe hypertension occurred in three patients with advanced chronic kidney disease and bilateral renal artery stenosis. After the introduction of ramipril, an initial fall in blood pressure was followed by a paradoxical increase in blood pressure. This was postulated to be caused by activation of the renin-angiotensin-aldosterone system, as a result of renal artery stenosis and renal dysfunction [55 ]. 

Chronic consumption of GA has been reported to be associated with corticosteroidlike effects and changes in cortisol metabolism in tissues which may lead to hypermineralocorticoid-like effects such as electrolyte imbalance, hypertension, and depression of the renin-angiotensin-aldosterone system [1, 2]. However, the effects are reversible upon withdrawal of GA [1]. 

Blood pressure (BP) and hypertension associated with Pb exposure appear to be related to toxic Pb effects on vascular reactivity, oxidative stress responses, and the renin—angiotensin—aldosterone system (RAAS). 

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

Abbreviations NSAID = nonsteroidal anti-inflammatory drugs, PG = prostaglandin, RBF = renal blood flow, GFR = glomerular filtration rate,HTN = hypertension, DM = diabetes mellitus, = potassium, RAA = renin-angiotensin- aldosterone, CHF = congestive heart failure, AGE = angiotensin-converting enzyme, SLF = systemic lupus erythematosis. 

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