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Additive amelioration of oxidative stress and cardiac function by combined mineralocorticoid and angiotensin receptor blockers in postinfarct failing hearts.
J Cardiovasc Pharmacol. 2012 Aug; 60(2):140-9.JC

Abstract

Reactive oxygen species are exacerbating factors in failing hearts. We examined whether spironolactone, a mineralocorticoid receptor antagonist, provides additional effects to olmesartan, an angiotensin II receptor blocker, on oxidative stress in postinfarct failing hearts. Congestive heart failure due to myocardial infarction (MI) was induced by the coronary artery ligation in rats. Three weeks later, the rats were divided into 4 groups: an untreated MI group, spironolactone (100 mg·kg·d)-treated MI group, olmesartan (10 mg·kg·d)-treated MI group, and combination-treated (spironolactone and olmesartan) MI group. After 7 weeks of MI, monotherapy improved left ventricular dilatation and function, and suppressed myocardial lipid peroxidation, in association with an attenuation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent and mitochondrial superoxide production. Moreover, combination therapy caused a synergistic improvement in these indices. In experiments using cultured myocytes, aldosterone (100 nmole/L) and angiotensin II (100 nmole/L) enhanced both sources of superoxide production, although these humoral factors affected NADPH oxidase subunits (p47phox and gp91phox) differently. In conclusion, aldosterone and angiotensin II increase NADPH oxidase-dependent and mitochondrial superoxide production in myocytes, and the combination of an angiotensin II receptor blocker and mineralocorticoid receptor antagonist has a synergistic attenuation of cardiac oxidative stress, leading to an improvement in cardiac function in postinfarct failing hearts.

Authors+Show Affiliations

Department of Clinical Pharmacology, Division of Pathological Science, Kyoto Pharmaceutical University, Kyoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

22549451

Citation

Noda, Kazuki, et al. "Additive Amelioration of Oxidative Stress and Cardiac Function By Combined Mineralocorticoid and Angiotensin Receptor Blockers in Postinfarct Failing Hearts." Journal of Cardiovascular Pharmacology, vol. 60, no. 2, 2012, pp. 140-9.
Noda K, Kobara M, Hamada J, et al. Additive amelioration of oxidative stress and cardiac function by combined mineralocorticoid and angiotensin receptor blockers in postinfarct failing hearts. J Cardiovasc Pharmacol. 2012;60(2):140-9.
Noda, K., Kobara, M., Hamada, J., Yoshifuji, Y., Shiraishi, T., Tanaka, T., Wang, J., Toba, H., & Nakata, T. (2012). Additive amelioration of oxidative stress and cardiac function by combined mineralocorticoid and angiotensin receptor blockers in postinfarct failing hearts. Journal of Cardiovascular Pharmacology, 60(2), 140-9. https://doi.org/10.1097/FJC.0b013e318258f8ce
Noda K, et al. Additive Amelioration of Oxidative Stress and Cardiac Function By Combined Mineralocorticoid and Angiotensin Receptor Blockers in Postinfarct Failing Hearts. J Cardiovasc Pharmacol. 2012;60(2):140-9. PubMed PMID: 22549451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Additive amelioration of oxidative stress and cardiac function by combined mineralocorticoid and angiotensin receptor blockers in postinfarct failing hearts. AU - Noda,Kazuki, AU - Kobara,Miyuki, AU - Hamada,Junichi, AU - Yoshifuji,Yusuke, AU - Shiraishi,Tatsuya, AU - Tanaka,Takuya, AU - Wang,Jiahong, AU - Toba,Hiroe, AU - Nakata,Tetsuo, PY - 2012/5/3/entrez PY - 2012/5/3/pubmed PY - 2012/12/27/medline SP - 140 EP - 9 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 60 IS - 2 N2 - Reactive oxygen species are exacerbating factors in failing hearts. We examined whether spironolactone, a mineralocorticoid receptor antagonist, provides additional effects to olmesartan, an angiotensin II receptor blocker, on oxidative stress in postinfarct failing hearts. Congestive heart failure due to myocardial infarction (MI) was induced by the coronary artery ligation in rats. Three weeks later, the rats were divided into 4 groups: an untreated MI group, spironolactone (100 mg·kg·d)-treated MI group, olmesartan (10 mg·kg·d)-treated MI group, and combination-treated (spironolactone and olmesartan) MI group. After 7 weeks of MI, monotherapy improved left ventricular dilatation and function, and suppressed myocardial lipid peroxidation, in association with an attenuation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent and mitochondrial superoxide production. Moreover, combination therapy caused a synergistic improvement in these indices. In experiments using cultured myocytes, aldosterone (100 nmole/L) and angiotensin II (100 nmole/L) enhanced both sources of superoxide production, although these humoral factors affected NADPH oxidase subunits (p47phox and gp91phox) differently. In conclusion, aldosterone and angiotensin II increase NADPH oxidase-dependent and mitochondrial superoxide production in myocytes, and the combination of an angiotensin II receptor blocker and mineralocorticoid receptor antagonist has a synergistic attenuation of cardiac oxidative stress, leading to an improvement in cardiac function in postinfarct failing hearts. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/22549451/Additive_amelioration_of_oxidative_stress_and_cardiac_function_by_combined_mineralocorticoid_and_angiotensin_receptor_blockers_in_postinfarct_failing_hearts_ L2 - https://doi.org/10.1097/FJC.0b013e318258f8ce DB - PRIME DP - Unbound Medicine ER -