Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury
| Autor: | James M. Luther, Nancy J. Brown, Samuel E. Cohen, Pengcheng Luo, Zuofei Wang, Agnes B. Fogo, Hyung-Suk Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Aldosterone synthase
Angiotensin receptor Time Factors Kidney Glomerulus Blood Pressure Spironolactone Renin-Angiotensin System Mice chemistry.chemical_compound Mineralocorticoid receptor Aldosterone Aorta Mineralocorticoid Receptor Antagonists biology cardiovascular Angiotensin II Nephrology Kidney Diseases hormones hormone substitutes and hormone antagonists medicine.medical_specialty hypertension renal injury Mice 129 Strain Heart Diseases medicine.drug_class Internal medicine Renin–angiotensin system medicine Animals Cytochrome P-450 CYP11B2 Vascular Diseases Sodium Chloride Dietary Inflammation Angiotensin II receptor type 1 business.industry urogenital system Myocardium angiotensin Fibrosis Mice Inbred C57BL Disease Models Animal Receptors Mineralocorticoid Endocrinology Gene Expression Regulation chemistry Mineralocorticoid biology.protein business Biomarkers |
| DOI: | 10.17615/98qm-dn94 |
| Popis: | Angiotensin II causes cardiovascular injury in part by aldosterone-induced mineralocorticoid receptor activation, and it can also activate the mineralocorticoid receptor in the absence of aldosterone in vitro. Here we tested whether endogenous aldosterone contributes to angiotensin II/salt-induced cardiac, vascular, and renal injury by the mineralocorticoid receptor. Aldosterone synthase knockout mice and wild-type littermates were treated with angiotensin II or vehicle plus the mineralocorticoid receptor antagonist spironolactone or regular diet while drinking 0.9% saline. Angiotensin II/salt caused hypertension in both the knockout and wild-type mice, an effect significantly blunted in the knockout mice. Either genetic aldosterone deficiency or mineralocorticoid receptor antagonism reduced cardiac hypertrophy, aortic remodeling, and albuminuria, as well as cardiac, aortic, and renal plasminogen activator inhibitor-1 mRNA expression during angiotensin II treatment. Mineralocorticoid receptor antagonism reduced angiotensin II/salt-induced glomerular hypertrophy, but aldosterone deficiency did not. Combined mineralocorticoid receptor antagonism and aldosterone deficiency reduced blood urea nitrogen and restored nephrin immunoreactivity. Angiotensin II/salt also promoted glomerular injury through the mineralocorticoid receptor in the absence of aldosterone. Thus, mineralocorticoid antagonism may have protective effects in the kidney beyond aldosterone synthase inhibition. |
| Databáze: | OpenAIRE |
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