Aldosterone cardiovascular effects

Davis KL, Nappi JM. The cardiovascular effects of eplerenone, a new selective aldosterone receptor antagonist. CUn Ther 2003 25 2647-2668. 

CARDIOVASCULAR SYSTEM The most striking cardiovascular effects of corticosteroids result from mineralocorticoid-induced changes in renal Na+ excretion, as is evident in primary aldosteronism. The resultant hypertension can lead to a diverse group of adverse effects on the cardiovascular system (see Chapter 32). Consistent with the known actions of mineralocorticoids in the kidney, restriction of dietary Na can lower the blood pressure considerably in mineralocorticoid excess. 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

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. 

Hence, ACE inhibitors reduce the detrimental effects of excess angiotensin II and aldosterone, and prolong the beneficial effects of bradykinin. These effects work in combination to sustain cardiovascular health in people with heart failure. 

It has also been suggested that certain diuretics such as spironolactone (Aldactone) might be especially helpful in heart failure.14,42 Spironolactone blocks aldosterone receptors in the kidneys and other tissues, thereby producing a diuretic effect as well as preventing adverse cardiovascular changes associated with excess aldosterone production. Future studies will help clarify whether spironolactone should be used preferentially in heart failure because of its ability to reduce fluid volume and protect against aldosterone-induced damage.53... 

Spironolactone induced a marked and statistically significant inhibitory effect on the cardiovascular reactivity to both the adrenergic and the rennin-angiotensin-aldosterone systems. This may play a major role in the vascular and antihypertensive properties of the drug [68],... 

Rocha R, StierCT Jr. Pathophysiological effects of aldosterone in cardiovascular tissues. Trends Endocrinol Metab 2001 12 308-14. 

Losartan blocks the vascular constrictor effect of Ang II, the Ang Il-induced aldosterone synthesis and/or release, and the All-induced cardiovascular growth. In various models of experimental hypertension, losartan prevents or reverses the elevated blood pressure and the associated cardiovascular hypertrophy similar to angiotensin converting enzyme (ACE) inhibitors. Subsequently con-tolled clinical trials revealed that losartan is a new and valuable drug for treatment of hyper-... 

Angiotensin II is involved in the renin-angiotensin-aldosterone system, which regulates blood pressure, sodium and water homoeostasis by the kidneys, and cardiovascular function. Angiotensin II stimulates the synthesis and secretion of aldosterone and raises blood pressure via a direct vasoconstrictor effect. 

An increasing number of studies are being conducted to evaluate the effects of aldosterone receptor antagonists on the progression of cardiovascular and renal disease and in the treatment of hypertension. Aldosterone receptor antagonists are commonly... 

A number of mechanisms has been postulated to explain the effects of Cd on the cardiovascular system, e.g. interference with catecholamine metabolism (inhibition of MAO-activity), direct action on vascular walls changing peripheral compliance or modifying responses to endogeneous pressor substances, modification of cardiac performance and involvement of the renin-angiotensin-aldosteron system, possibly triggered by changes in sodium reabsorption. 

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