eplerenone and Vascular-Diseases

Aldosterone has a variety of detrimental effects on the heart and vasculature and is increasingly recognized as an important target in chronic heart failure, as illustrated by the Randomized Aldactone Evaluation Study. In this article, the evidence supporting the cardiovascular effects of aldosterone in humans and the proven benefits of aldosterone-receptor antagonists in heart failure shall be discussed.

Topics: Aldosterone; Autonomic Nervous System Diseases; Endomyocardial Fibrosis; Eplerenone; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone; Vascular Diseases; Water-Electrolyte Imbalance

A 50-year-old man was referred to our hospital for colitis with abdominal pain and diarrhea that had persisted for more than 8 months. 9 months earlier, he had been treated for fulminant eosinophilic myocarditis. During steroid therapy, ulceration appeared in the esophagus, stomach and large intestine. The biopsy results showed cytomegalovirus (CMV) inclusion bodies, and the patient was diagnosed with CMV gastrocolitis and treated with ganciclovir. Colonoscopy 7 months earlier revealed ischemia-like segmental colitis 10 cm in length in the hepatic flexure without evidence of CMV infection. Colonoscopy after 1 month and 3 months showed no improvement. We suspected drug-induced focal ischemic colitis, and discontinued eplerenone. Colonoscopy 2 months after withdrawal of eplerenone showed improvement in colitis, and colonoscopy 8 months later showed ulcer healing. Venous disorders are cautioned as a known side effect of eplerenone, but this is the first report of venous stasis colitis thought to be caused by eplerenone.

Topics: Antiviral Agents; Colitis; Colonoscopy; Cytomegalovirus; Cytomegalovirus Infections; Eplerenone; Ganciclovir; Humans; Male; Middle Aged; Vascular Diseases

Previous experiments have studied separately the development of either cardiac or aortic fibrosis and stiffness in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine in vivo the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on simultaneous changes in cardiac and arterial structure and function and their interactions.. Aldo was administered in uninephrectomised Sprague-Dawley rats receiving a high-salt diet from 8 to 12 weeks of age. Three groups of Aldo-salt rats were treated with 1 to 100 mg/kg-1. d-1 Epl by gavage. Arterial elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The cardiac and arterial walls were analysed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo caused increased systolic blood pressure (SBP), carotid Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities. No difference in collagen mRNA levels was detected between groups. During the same period, cardiac mass and collagen mRNA and protein levels increased markedly in the myocardial tissue. Epl normalised collagen in the myocardium, Eincwall stress curves, MCSA, and EIIIA Fn in Aldo rats. These dose-dependent effects were not accompanied by a consistent reduction in SBP and cardiac mass.. In exogenous hyperaldosteronism in the rat, Aldo causes independently myocardial collagen and arterial Fn accumulation, the latter being responsible for increased intrinsic carotid stiffness. Epl prevents both cardiac and arterial effects but does not reduce consistently SBP.

Topics: Animals; Aorta; Blood Pressure; Blotting, Northern; Carotid Artery Diseases; Collagen; Eplerenone; Fibrosis; Heart Diseases; Hypertension; Immunohistochemistry; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Rats; Rats, Sprague-Dawley; RNA, Messenger; Spironolactone; Structure-Activity Relationship; Vascular Diseases

Topics: Administration, Oral; Animals; Calcinosis; Eplerenone; Humans; Kidney Failure, Chronic; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Osteopontin; Rats; Renal Dialysis; Sialoglycoproteins; Spironolactone; Vascular Diseases

To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury. Administration of angiotensin II and Nomega-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through administration of the selective aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage without significantly altering blood pressure. Aldosterone infusion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensin II induced vascular damage through mechanisms apparently independent of its effects on systolic blood pressure.

Topics: Adrenalectomy; Aldosterone; Angiotensin II; Animals; Blood Pressure; Cardiomyopathies; Enzyme Inhibitors; Eplerenone; Hormone Antagonists; Kidney; Male; Myocardium; Necrosis; NG-Nitroarginine Methyl Ester; Rats; Rats, Wistar; Renal Artery; Renin; Sodium Chloride; Spironolactone; Vascular Diseases