Tags

Type your tag names separated by a space and hit enter

Dual blockade of aldosterone and angiotensin II additively suppresses TGF-beta and NADPH oxidase in the hypertensive kidney.
Nephrol Dial Transplant. 2007 May; 22(5):1314-22.ND

Abstract

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)-beta 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-beta. Renal TGF-beta 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-beta resulting in improvement of renal damage.

Authors+Show Affiliations

Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17324946

Citation

Onozato, Maristela Lika, et al. "Dual Blockade of Aldosterone and Angiotensin II Additively Suppresses TGF-beta and NADPH Oxidase in the Hypertensive Kidney." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 22, no. 5, 2007, pp. 1314-22.
Onozato ML, Tojo A, Kobayashi N, et al. Dual blockade of aldosterone and angiotensin II additively suppresses TGF-beta and NADPH oxidase in the hypertensive kidney. Nephrol Dial Transplant. 2007;22(5):1314-22.
Onozato, M. L., Tojo, A., Kobayashi, N., Goto, A., Matsuoka, H., & Fujita, T. (2007). Dual blockade of aldosterone and angiotensin II additively suppresses TGF-beta and NADPH oxidase in the hypertensive kidney. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 22(5), 1314-22.
Onozato ML, et al. Dual Blockade of Aldosterone and Angiotensin II Additively Suppresses TGF-beta and NADPH Oxidase in the Hypertensive Kidney. Nephrol Dial Transplant. 2007;22(5):1314-22. PubMed PMID: 17324946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual blockade of aldosterone and angiotensin II additively suppresses TGF-beta and NADPH oxidase in the hypertensive kidney. AU - Onozato,Maristela Lika, AU - Tojo,Akihiro, AU - Kobayashi,Naohiko, AU - Goto,Atsuo, AU - Matsuoka,Hiroaki, AU - Fujita,Toshiro, Y1 - 2007/02/26/ PY - 2007/2/28/pubmed PY - 2007/8/10/medline PY - 2007/2/28/entrez SP - 1314 EP - 22 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 22 IS - 5 N2 - 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)-beta 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-beta. Renal TGF-beta 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-beta resulting in improvement of renal damage. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/17324946/Dual_blockade_of_aldosterone_and_angiotensin_II_additively_suppresses_TGF_beta_and_NADPH_oxidase_in_the_hypertensive_kidney_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfl780 DB - PRIME DP - Unbound Medicine ER -