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Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction.
Circulation. 2005 May 03; 111(17):2157-64.Circ

Abstract

BACKGROUND

The renin-angiotensin-aldosterone system is implicated in the pathogenesis of heart failure. Pharmacological blockade of angiotensin II (Ang II)-dependent signaling is clinically effective in reducing cardiovascular events after myocardial infarction (MI) but still fails to completely prevent remodeling. The molecular basis underlying this Ang II-independent remodeling is unclear.

METHODS AND RESULTS

Acute MI was induced by coronary ligation in wild-type (WT) and angiotensin II type IA receptor-knockout (AT1A-KO) mice. Left ventricular (LV) geometry, hemodynamics, and cardiac gene expression were evaluated on day 28. Severe LV remodeling and resultant cardiac dysfunction were observed in WT mice, whereas less marked, but still significant, LV remodeling and cardiac dysfunction were induced in AT1A-KO mice. Gene expression levels of aldosterone synthase and the cardiac aldosterone content were both elevated in the MI hearts, even in AT1A-KO mice. In AT1A-KO mice treated with spironolactone (20 mg/kg per day), LV remodeling, cardiac dysfunction, and cardiac gene expression of collagens and natriuretic peptides were almost normalized.

CONCLUSIONS

Our results indicate that genetic blockade of AT1A signaling fails to arrest aldosterone production in cardiac tissues and that cardiac aldosterone plays a critical role in post-MI LV remodeling. The results suggest that spironolactone could be potentially effective in patients with MI, when used in combination with renin-angiotensin system blockade, by blocking the actions of aldosterone produced by Ang II-independent mechanisms.

Authors+Show Affiliations

Pfizer-KEIO Research Laboratory, Tokyo, Japan. katada@kt.rim.or.jpNo 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

15851599

Citation

Katada, Jun, et al. "Persistent Cardiac Aldosterone Synthesis in Angiotensin II Type 1A Receptor-knockout Mice After Myocardial Infarction." Circulation, vol. 111, no. 17, 2005, pp. 2157-64.
Katada J, Meguro T, Saito H, et al. Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction. Circulation. 2005;111(17):2157-64.
Katada, J., Meguro, T., Saito, H., Ohashi, A., Anzai, T., Ogawa, S., & Yoshikawa, T. (2005). Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction. Circulation, 111(17), 2157-64.
Katada J, et al. Persistent Cardiac Aldosterone Synthesis in Angiotensin II Type 1A Receptor-knockout Mice After Myocardial Infarction. Circulation. 2005 May 3;111(17):2157-64. PubMed PMID: 15851599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction. AU - Katada,Jun, AU - Meguro,Tomomi, AU - Saito,Hitomi, AU - Ohashi,Akira, AU - Anzai,Toshihisa, AU - Ogawa,Satoshi, AU - Yoshikawa,Tsutomu, Y1 - 2005/04/25/ PY - 2005/4/27/pubmed PY - 2005/12/28/medline PY - 2005/4/27/entrez SP - 2157 EP - 64 JF - Circulation JO - Circulation VL - 111 IS - 17 N2 - BACKGROUND: The renin-angiotensin-aldosterone system is implicated in the pathogenesis of heart failure. Pharmacological blockade of angiotensin II (Ang II)-dependent signaling is clinically effective in reducing cardiovascular events after myocardial infarction (MI) but still fails to completely prevent remodeling. The molecular basis underlying this Ang II-independent remodeling is unclear. METHODS AND RESULTS: Acute MI was induced by coronary ligation in wild-type (WT) and angiotensin II type IA receptor-knockout (AT1A-KO) mice. Left ventricular (LV) geometry, hemodynamics, and cardiac gene expression were evaluated on day 28. Severe LV remodeling and resultant cardiac dysfunction were observed in WT mice, whereas less marked, but still significant, LV remodeling and cardiac dysfunction were induced in AT1A-KO mice. Gene expression levels of aldosterone synthase and the cardiac aldosterone content were both elevated in the MI hearts, even in AT1A-KO mice. In AT1A-KO mice treated with spironolactone (20 mg/kg per day), LV remodeling, cardiac dysfunction, and cardiac gene expression of collagens and natriuretic peptides were almost normalized. CONCLUSIONS: Our results indicate that genetic blockade of AT1A signaling fails to arrest aldosterone production in cardiac tissues and that cardiac aldosterone plays a critical role in post-MI LV remodeling. The results suggest that spironolactone could be potentially effective in patients with MI, when used in combination with renin-angiotensin system blockade, by blocking the actions of aldosterone produced by Ang II-independent mechanisms. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15851599/Persistent_cardiac_aldosterone_synthesis_in_angiotensin_II_type_1A_receptor_knockout_mice_after_myocardial_infarction_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000163562.82134.8E?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -