Journal Article10.1097/00132980-200508000-00009
Aldosterone and end-organ damage
186
TL;DR: Better understanding of the mineralocorticoid receptor-independent effects of aldosterone, the role of nonaldosterone mineralocortex receptor agonists, and the mechanisms involved in the progression from inflammation to fibrosis and remodeling would enable the development of new strategies to slow the progression of cardiovascular and renal disease.
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Abstract: Purpose of review This review highlights recent clinical studies demonstrating the contribution of aldosterone to cardiovascular mortality, vascular dysfunction, and renal injury in the context of advances in our understanding of the molecular biology of aldosterone. Recent findings Mineralocorticoid receptor antagonism reduces mortality in patients with congestive heart failure and following myocardial infarction. Studies in animal models and in patients with congestive heart failure or hypertension indicate that aldosterone induces oxidative stress and impairs endothelial nitric oxide synthase through a mineralocorticoid receptor-dependent mechanism. Furthermore, aldosterone can cause vasoconstriction and vasodilation through rapid nongenomic mechanisms. The contribution of the nongenomic effects of aldosterone to vascular tone may depend on underlying endothelial function. In the heart and kidney, aldosterone stimulates oxidative stress and increases expression of inflammatory markers leading to fibrosis. The induction of inflammation and fibrosis appears to be both sodium and mineralocorticoid receptor dependent. The mechanisms underlying the progression from inflammation to fibrosis remain to be elucidated. Studies measuring circulating markers of collagen turnover suggest that mineralocorticoid antagonism reduces extracellular matrix turnover and cardiac remodeling in humans as well. Similarly, mineralocorticoid receptor antagonism reduces urinary albumen excretion in clinical trials in humans. Summary Aldosterone induces oxidative stress, endothelial dysfunction, inflammation and fibrosis in the vasculature, heart and kidney. While most of these effects appear to be mediated via the mineralocorticoid receptor, better understanding of the mineralocorticoid receptor-independent effects of aldosterone, the role of nonaldosterone mineralocorticoid receptor agonists, and the mechanisms involved in the progression from inflammation to fibrosis and remodeling would enable the development of new strategies to slow the progression of cardiovascular and renal disease.
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Felix José Alvarez Ramires,Antonio de Pádua Mansur,Otávio Rizzi Coelho,Mario Maranhão,Gruppi C,Charles Mady,José Antonio Franchini Ramires +6 more
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Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo
Nancy J. Brown,Shinya Nakamura,Li-Jun Ma,Ikuko Nakamura,Ellen Donnert,Michael L. Freeman,Douglas E. Vaughan,Agnes B. Fogo +7 more
TL;DR: This study is, to the authors' knowledge, the first to demonstrate that aldosterone regulates PAI-1 expression in vivo, and supports the hypothesis that a Aldosterone induces renal injury through its effects on PAI/GAPDH expression.
Possible Contributions of Reactive Oxygen Species and Mitogen-Activated Protein Kinase to Renal Injury in Aldosterone/Salt-Induced Hypertensive Rats
Akira Nishiyama,Li Yao,Yukiko Nagai,Kayoko Miyata,Masanori Yoshizumi,Shoji Kagami,Shoji Kagami,Shuji Kondo,Hideyasu Kiyomoto,Takatomi Shokoji,Shoji Kimura,Shoji Kimura,Masakazu Kohno,Youichi Abe +13 more
TL;DR: It is suggested that ROS and MAPK play a role in the progression of renal injury induced by chronic elevations in aldosterone, and eplerenone and tempol treatments normalized the activities of ERK1/2, JNK, and BMK1.
The serum- and glucocorticoid-induced kinase is a physiological mediator of aldosterone action.
Aditi Bhargava,Meryl J. Fullerton,Kathy Myles,Timothy M Purdy,John W. Funder,David A. Pearce,Tim J Cole +6 more
TL;DR: The early onset of SGK induction in kidney and colon and the correlation with urinary changes in terms of both time course and dose response suggest that SGK plays an important role in mediating the effects of aldosterone on sodium homeostasis in vivo.