Dual blockade of aldosterone and angiotensin II additively suppresses TGF- and NADPH oxidase in the hypertensive kidney
| Autor: | Toshiro Fujita, Akihiro Tojo, Hiroaki Matsuoka, Maristela L. Onozato, Atsuo Goto, Naohiko Kobayashi |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Indoles medicine.drug_class Cardiac Output Low Angiotensin-Converting Enzyme Inhibitors Spironolactone Kidney chemistry.chemical_compound Transforming Growth Factor beta Internal medicine Animals Medicine cardiovascular diseases Aldosterone Mineralocorticoid Receptor Antagonists Transplantation Rats Inbred Dahl NADPH oxidase biology Superoxide Dismutase business.industry Angiotensin II NADPH Oxidases Kidney metabolism Drug Synergism Eplerenone Rats Oxidative Stress Endocrinology chemistry Nephrology Mineralocorticoid Hypertension ACE inhibitor biology.protein Sodium-Potassium-Exchanging ATPase Reactive Oxygen Species business Nicotinamide adenine dinucleotide phosphate medicine.drug |
| Zdroj: | Nephrology Dialysis Transplantation. 22:1314-1322 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfl780 |
| Popis: | Background. Angiotensin II blockade and spironolactone effectively reduces proteinuria in humans. To clarify the mechanisms of the beneficial effect of blockade of both aldosterone and angiotensin II, we associated the aldosterone antagonist eplerenone to an angiotensin-converting enzyme inhibitor (ACEI) and examined the effect on renal transforming growth factor (TGF)-b expression and oxidative stress by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the Dahl salt-sensitive rat with heart failure (DSHF). Methods. Dahl salt-resistant control rats and DSHF rats were fed with 8% NaCl diet and at 11 weeks the DSHF rats were treated with vehicle, eplerenone (Epl), trandolapril or a combination of both drugs for 7 weeks. Results. DSHF rats showed increased NADPH oxidase and decreased superoxide dismutase (SOD) resulting in increased oxidative stress. ACEI and Epl reduced NADPH oxidase showing an additive effect in their combination; ACEI increased manganese SOD (MnSOD) and Epl increased MnSOD, copper–zinc SOD and catalase, resulting in the lowest levels of oxidative stress with the combination therapy. Glomerulosclerosis and proteinuria were increased in the DSHF rats, and Epl suppressed them more effectively than ACEI to levels not different from the combination of both, showing a positive correlation with NADPH oxidase expression and TGF-b. Renal TGF-b was specifically suppressed with Epl Conclusion. The association of Epl to ACEI is beneficial due to further reduction of NADPH oxidase and specific inhibition of TGF-b resulting in improvement of renal damage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|