Aldosterone, production, angiotensin

Angiotensin II is a neurohormone produced primarily in the kidney. It is a potent vasoconstrictor and stimulates the production of aldosterone. Together, angiotensin II and aldosterone increase blood pressure and sodium and water retention (increasing ventricular wall tension), cause endothelial dysfunction, promote blood clot formation, and cause myocardial fibrosis. 

As previously discussed, increased portal pressure triggers the release of nitric oxide to directly vasodilate the splanchnic arterial bed and decrease portal pressure. Unfortunately, nitric oxide also dilates the systemic arterial system, causing a decrease in blood pressure and a decrease in renal perfusion by lowering the effective intravascular volume. The kidney reacts by activating the renin-angiotensin-aldosterone system, which increases plasma renin activity, aldosterone production, and sodium retention. This increase in intravascular volume furthers the imbalance of intravascular oncotic pressure, allowing even more fluid to escape to the extravascular spaces. 

Diuretics are often required in addition to the sodium restriction described previously. Spironolactone and jurosemide form the basis of pharmacologic therapy for ascites. Spironolactone is an aldosterone antagonist and counteracts the effects of activation of the renin-angiotensin-aldosterone system. In hepatic disease not only is aldosterone production increased, but its half-life is prolonged because it is hepatically metabolized. Spironolactone acts to conserve the potassium that would be otherwise excreted because of elevated aldosterone levels. 

The zona glomerulosa is responsible for the production of the mineralocorticoids aldosterone, deoxycorticosterone, and 18-hydroxy-deoxycorticosterone. Aldosterone promotes renal sodium retention and excretion of potassium. Its synthesis and release are regulated by renin in response to decreased vascular volume and renal perfusion. Adrenal aldosterone production is regulated by the renin-angiotensin-aldosterone system. 

Autonomic and hormonal control of cardiovascular function. Note that two feedback loops are present the autonomic nervous system loop and the hormonal loop. The sympathetic nervous system directly influences four major variables peripheral vascular resistance, heart rate, force, and venous tone. It also directly modulates renin production (not shown). The parasympathetic nervous system directly influences heart rate. In addition to its role in stimulating aldosterone secretion, angiotensin II directly increases peripheral vascular resistance and facilitates sympathetic effects (not shown). The net feedback effect of each loop is to compensate for changes in arterial blood pressure. Thus, decreased blood pressure due to blood loss would evoke increased sympathetic outflow and renin release. Conversely, elevated pressure due to the administration of a vasoconstrictor drug would cause reduced sympathetic outflow, reduced renin release, and increased parasympathetic (vagal) outflow. 

NOTE Aldosterone production requires the renin-angiotension system Renin is an enzyme secreted by the juxtaglomerular ceils of the kidney in response to decreased arterial blood pressure and blood flow. Renin stimulates conversion of the protein angiotensinogen to angiotensin I which then becomes angiotensin II. Angiotensin II stimulates the synthesis and release of aldosterone by the adrenal cortex. 

This occurs in hypopituitarism. In theory the best treatment is corticotropin, but the disadvantages of frequent injection are such that hydrocortisone is preferred. Usually less hydrocortisone is needed than in primary insufficiency. Special sodium-retaining hormone is seldom required, for the pituitary has little control over aldosterone production which responds principally to plasma potassium concentration and to the renin-angiotensin system. Thyroxine and sex hormones are given when appropriate. The general conduct of therapy does not differ significantly from that in primary adrenal insufficiency. 

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. 

Fig. 2 (a, b) Cortisol and aldosterone production were measured over 48 h in response to physiological stimuli (n=2 experiments). K+ signifies an increase in potassium from 4 to 10 mM ACTH = 10 nM, Angiotensin 11 = 100 nM. (c, d) Exposures to etomidate, ketoconazole, or resveratrol (n= 3 experiments, means shown SEM). Significant difference relative to 10 pM forskolin treatments (mean shown as upper dotted line) as determined by one-way ANOVA. Lower dotted line shows mean cortisol levels produced without stimulation... 

The excess production of 11-deoxycorticosterone and corticosterone by infants with an 18-oxidation defect is probably due to an excess production of angiotensin, the stimulant for aldosterone production (M20). Renin, produced by the juxtaglomerular cells in the kidneys, initiates the formation of angiotensin, and a loss of salt causes this substance to be produced in excessive amounts. Evidence for this has been obtained by Ulick et al. (Ul), who found an increased amount of renin in the plasma of their patients during sodium depletion experiments. 

ACE inhibitors and angiotensin 11 receptor inhibitors limit the action of angiotensin II and suppress aldosterone production. These effects have benefits in the treatment of cardiac failure and hypertension because the resulting vasodilation and water loss lowers blood pressure. 

The primary stimulus for aldosterone production is the octapeptide angiotensin 11, although hyperkalemia (greater than normal levels of potassium in the blood) or hyponatremia (less than normal levels of sodium in the blood) may directly stimulate aldosterone synthesis as well. ACTH has a permissive action in aldosterone production. It allows cells to respond optimally to their primary stimulus, angiotensin 11. 

Hyperkalemia should not be treated with drugs that interfere with aldosterone production (eg, losartan, an angiotensin II receptor blocker) or collecting tubule potassium excretion (eg, amiloride, spironolactone, triamterene). These agents are all capable of increasing serum potassium. Hydrochlorothiazide would not reduce serum potassium rapidly, but it would not increase it. The answer is (B). 

Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II to decrease vasoconstriction this drug also will prevent aldosterone production and sodium and water retention. 

Deta nonoate [2,2 (hydroxynitrosohydrazono)his-ethanamine], a zwitterion nitric oxide donor, potently inhibited forskohn- and angiotensin II-stimulated aldosterone production in human adrenocortical H295R cells in a concentration-depen-dent manner (Kreklau et al. 1999). 

See also aldosterone production rate, aldosteronism, renin-angiotensin sytem... 

An octopeptide hormone which is produced as a result of the action of a peptidase on angiotensin I. Its two main actions are the stimulation of aldosterone production from the adrenal cortex, and an action on the blood vessel walls causing vasoconstriction. It can be measured by radioimmunoassay. 

Renin assays can be useful in distinguishing between primary and secondary aldosteronism. It can be measured by its enzymic action on angiotensinogen, the product, angiotensin I, being measured by radioimmunoassay. 

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