Spironolactone Modulates Expressions of Cardiac Mineralocorticoid Receptor and 11.BETA.-Hydroxysteroid Dehydrogenase 2 and Prevents Ventricular Remodeling in Post-Infarct Rat Hearts

Abstract

Aldosterone antagonists have been reported to prevent ventricular remodeling after myocardial infarction (MI) via their action to extracellular matrix (ECM).

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

“…-in the heart of rodents with myocardial infarction (Milik et al, 2007;Takeda et al, 2007), with diastolic heart failure (Ohtani et al, 2007), or with hypertension (Silvestre et al, 2000;Konishi et al, 2003); -in vessels of hypertensive animals (SHR) (DeLano and Schmid-Schonbein, 2004) or vascular cells in a model of normal aging (30-month-old Fisher344 cross-bred Brown Norway rats) (Krug et al, 2010); -in hypoxic pulmonary artery vascular endothelial cells (Maron et al, 2014); -in the kidney of Brown Norway rats (Cavallari et al, 2008) and in the renal collecting duct of spontaneously hypertensive rats (Farman and Bonvalet, 1985); -in adipose tissue from diabetic animal models (obese db/db and ob/ob mice, HFD) (Guo et al, 2008;Hirata et al, 2009Hirata et al, , 2012; in kidney from db/db mice and streptozotocin-treated rats (Guo et al, 2006); -in skin of mice with ultraviolet irradiation and metabolic syndrome .…”

Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis

“…23 Two-millimeter-long aortic rings cleaned of fat were mounted on a wire myograph (DMT, Aarhus, Denmark). Endothelial function was determined according to the protocol previously described.…”

Mineralocorticoid Receptor Activation and Mineralocorticoid Receptor Antagonist Treatment in Cardiac and Renal Diseases

“…Safety data on the use of MRAs in patients with end-stage renal disease undergoing hemodialysis suggest that the risk of hyperkalemia with low-dose MRAs is significantly lower than previously thought, and MRA treatment with close laboratory monitoring is a favorable treatment option in these patients. 2 A recent randomized controlled trial in patients with oliguria undergoing hemodialysis demonstrated substantial reductions in cardiovascular and cerebrovascular mortality and morbidity with spironolactone compared with controls, providing a strong rationale for further investigations in large-scale clinical trials (Table S3).…”

“…1 Aldosterone is a steroid hormone with mineralocorticoid activity, produced primarily in the glomerular zone of the adrenal cortex. 2 Aldosterone fulfills its major physiological function of maintaining sodium and potassium balance and blood pressure control by binding to the mineralocorticoid receptor (MR) in the connecting tubule and cortical collecting duct in the kidneys, thereby increasing sodium reabsorption and potassium secretion. There is a growing body of evidence for a broader role of aldosterone and MR activation in the pathophysiology of cardiovascular and renal disease.…”