Clinical Note

Persons with a genetic defect in HSD-II suffer from symptoms of mineralocorticoid excess (hypertension and hypokalemia) as a result of constant saturation of the mineralo-corticoid receptor by cortisol. An acquired form of the same ailment is seen after ingestion of excessive amounts of licorice, which contains the potent inhibitors of HSD, glycyrrhizic acid and its metabolite glycyrrhetinic acid.

Angiotensin II is the primary stimulus for aldosterone secretion, although ACTH and high concentrations of potassium are also potent stimuli. Angiotensin II is formed in blood by a two-step process that depends on proteolytic cleavage of the plasma protein, angiotensino-gen, by the enzyme renin, to release the inactive decapep-tide angiotensin I. Angiotensin I is then converted to angiotensin II by the ubiquitous angiotensin-converting enzyme. Control of angiotensin II production is achieved by regulating the secretion of renin from smooth muscle cells of the afferent glomerular arterioles. The principal stimulus for renin secretion is a decrease in the vascular volume, and the principal physiologic role of aldosterone is to defend the vascular volume. Aldosterone secretion is regulated by negative feedback, with vascular volume, not the concentration of aldosterone, as the controlled variable. Reabsorption of sodium is accompanied by a proportionate reabsorption of water, and because sodium remains extracellular, sodium retention expands the extracellular volume and hence blood volume. Expansion of the blood volume, which is the ultimate result of sodium retention, provides the negative feedback signal for regulation of renin and aldosterone secretion (Fig. 11). Although preservation of body sodium is central to aldosterone action, the concentration of sodium in blood does not appear to be monitored directly, and fluctuations in plasma concentrations have little direct effect on the secretion of renin.

increased blood volume kidney ■ '

duct

aldosterone duct kidney ■ '

adrenal zona glomerulosa adrenal zona glomerulosa angiotensinogen angiotensin II

angiotensin I

FIGURE 11 Negative feedback control of aldosterone secretion. The monitored variable is blood volume. ( + ), stimulates; (—), inhibits.

Even if sodium balance could be preserved and carbohydrate intake were adequate to meet energy needs, individuals suffering from adrenal insufficiency would still teeter on the brink of disaster when faced with a threatening environment. We consider here only the most thoroughly studied actions of glucocorticoids.

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