Aldosterone effects

ACE inhibitors are approved for the treatment of hypertension and cardiac failure [5]. For cardiac failure, many studies have demonstrated increased survival rates independently of the initial degree of failure. They effectively decrease work load of the heart as well as cardiac hypertrophy and relieve the patients symptoms. In contrast to previous assumptions, ACE inhibitors do not inhibit aldosterone production on a long-term scale sufficiently. Correspondingly, additional inhibition of aldosterone effects significantly reduces cardiac failure and increases survival even further in patients already receiving diuretics and ACE inhibitors. This can be achieved by coadministration of spironolactone, which inhibits binding of aldosterone to its receptor. 

Spironolactone inhibits aldosterone effects by competing with aldosterone for intracellular mineralocorticoid receptors. When spironolactone (or its active metabolites) binds to these receptors, the complex fails to translocate into the nucleus and/ or bind to the nuclear chromatin. All of the subsequent phases of the effects of aldosterone are therefore inhibited,... 

Because the control mechanisms that attempt to maintain blood pressure constant are intact in patients with pheochromocytoma (they are reset in patients with ordinary hypertension), a number of compensatory changes are observed in pheochromocytoma patients tsee Figure 6 ). These include reduced renin, angiotensin, and aldosterone levels in the blood. With the reduced aldosterone effect on the kidney, more salt and water is excreted, reducing blood volume. Since the red cell mass is not affected, hematocrit is often increased. If the tumor releases only norepinephrine, a compensatory bradycardia may also be present, but most patients release enough epinephrine to maintain heart rate at a normal or even increased level. 

Licorice is a flavoring for candy, but it is also used as an herbal medication in tablet, tea, or tincture form. Licorice increases the aldosterone effect, which helps treat Addison s disease. 

Biologic Significance of the Adrenal Cortex. The adrenocortical hormones constitute some of the most vital substances. Extirpation of the adrenal gland in experimental animals is followed by most serious disturbances and, in a few days, by death. Among other things, the metabolism of electrolytes is unbalanced (increased Na+ excretion). This effect can be reversed by administration of adrenocortical hormones, some of which (especially aldosterone) effect the retention of sodium and excretion of potassium (cf. Chapt. XXI-5). 

Spironolactone antagonizes the effects of aldosterone by binding at the aldosterone receptor in the cytosol of the late distal tubules and renal collecting ducts. Side effects of spironolactone are gynecomastia, decreased Hbido, and impotency. 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

With other acetylenes steric factors may be operative which render the selective reduction somewhat difficult. In the aldosterone intermediates (53) and (54), for instance, selective hydrogenation is obtained only with the 14 -acetylenic ether " (hydroxyl group effect). 

Induces dyskinesia/vasodilatation, schizophrenia/4- coordination Vaso constriction/cell proliferation/aldosterone secretion Vaso constriction/cell proliferation/bronchoconstriction 4-memory, sedation/vasodilatation/4 GI motility A blood pressure/4- GI secretion Vagal effects/A blood pressure/tachycardia... 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

Cyclic GMP is made from GTP by the enzyme gua-nylyl cyclase, which exists in soluble and membrane-bound forms. Each of these isozymes has unique physiologic properties. The atriopeptins, a family of peptides produced in cardiac atrial tissues, cause natriuresis, diuresis, vasodilation, and inhibition of aldosterone secretion. These peptides (eg, atrial natriuretic factor) bind to and activate the membrane-bound form of guanylyl cyclase. This results in an increase of cGMP by as much as 50-fold in some cases, and this is thought to mediate the effects mentioned above. Other evidence links cGMP to vasodilation. A series of compounds, including nitroprusside, nitroglycerin, nitric oxide, sodium nitrite, and sodium azide, all cause smooth muscle re-... 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

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