Renin-Angiotensin-Aldosterone Axis

Fig. 8. Regulation of renin-angiotensin-aldosterone axis. stimulation -I, inhibition.

Treatment with angiotensin-converting enzyme inhibitors is also more likely to be associated with hyperkalemia in older individuals (69). Impaired angiotensin II formation limits this potent stimulus for aldosterone secretion, and this is superimposed on the already age-related decrease in activity of the renin-angiotensin-aldosterone axis. The same drug-induced hyporeninemic hypoaldosteronism is predicted for the angiotensin receptor blockers. However, to date this has not been documented clincally. 

Diuretics are drugs that increase the rate of urine flow clinically useful diuretics also increase the rate of excretion of Na+ (natiiuresis) and an accompanying anion, usually CD. Most clinical applications of diuretics aim to reduce extracellular fluid volume by decreasing total-body NaCl content. Although continued administration of a diuretic causes a sustained net deficit in total-body Na+, the time course of natriuresis is finite because renal compensatory mechanisms bring Na+ excretion in line with Na+ intake, a phenomenon known as diuretic braking. Compensatory mechanisms include activation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone axis, decreased arterial blood pressure (which reduces pressure natriuresis), hypertrophy of renal epithelial cells, increased expression of renal epithelial transporters, and perhaps alterations in natriuretic hormones such as atrial natriuretic peptide. 

EFFECTS ON URINARY EXCRETION Loop diuretics profoundly increase the urinary excretion of Na+ and Cl" (i.e., up to 25% of the filtered load of Na+) and markedly increase the excretion of Ca + and Mg +. Furosemide but not bumetanide also has weak carbonic anhydrase-inhibiting activity that increases the urinary excretion of HCO " and phosphate. AU inhibitors of the Na+-K+-2CL symporter increase the urinary excretion of K+ and titratable acid, due in part to increased delivery of Na+ to the distal tubule. The mechanism by which increased distal delivery of Na+ enhances excretion of K+ and H+ is discussed in the section on inhibitors of Na+ channels. Other mechanisms contributing to enhanced K+ and H+ excretion include flow-dependent enhancement of ion secretion by the collecting duct, nonosmotic vasopressin release, and activation of the renin-angiotensin-aldosterone axis. Loop diuretics acutely increase the excretion of uric acid, whereas their chronic administration reduces uric acid excretion, possibly due to enhanced transport in the proximal tubule secondary to volume depletion or to competition between the diuretic and uric acid for the organic acid secretory mechanism in the proximal tubule. 

Epstein, M.T., E.A. Espiner, R.A. Donald, and H. Hughes. 1977. Effect of eating liquorice on the renin-angiotensin-aldosterone axis in normal subjects. Br. Med. J. l(6059) 488-890. 

Symptoms of overt beriberi are usually abrupt with presentation of left ventricular cardiac and peripheral vascular failure yielding water retention due to stimulation of the renin-angiotensin-aldosterone axis by hypovolemia, as well as striated and smooth muscles weakness in the wet form of the disease. At this stage of the disease, the clinical diagnosis is usually apparent but outcome of the supplementary treatment with thiamine may be poor, due to irreversible alterations in muscles and the central nervous system (CNS). 

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