Journal article
Blood Pressure Variability Activates Cardiac Mineralocorticoid Receptor and Induces Cardiac Remodeling in Hypertensive Rats
Circulation journal : official journal of the Japanese Circulation Society, Vol.77(6), pp.1474-1481
2013
DOI: 10.1253/circj.CJ-12-1253
PMID: 23470864
Abstract
Background: Hypertensive patients with large blood pressure variability (BPV) have aggravated target organ damage. Because the aldosterone/mineralocorticoid receptor (MR) system is a possible mechanism of hypertensive organ damage, we investigated in spontaneously hypertensive rats (SHRs) whether a specific MR blocker, eplerenone, would prevent BPV-induced aggravation of hypertensive cardiac remodeling.
Methods and Results: A rat model of a combination of hypertension and large BPV was created by performing bilateral sinoaortic denervation (SAD) in SHRs. SAD increased BPV without changing mean BP. SAD induced perivascular macrophage infiltration and aggravated myocardial fibrosis and cardiac hypertrophy, resulting in LV systolic dysfunction. Immunohistostaining revealed SAD-induced translocation of MRs into the nuclei (ie, MR activation) of the intramyocardial arterial medial cells and cardiac myocytes. SAD increased phosphorylation of p21-activated kinase1 (PAK1), a regulator of MR nuclear translocation. Chronic administration of a subdepressor dose of eplerenone prevented MR translocation, macrophage infiltration, myocardial fibrosis, cardiac hypertrophy, and LV dysfunction, while not affecting BPV. Circulating levels of aldosterone and cortisol were not changed by SAD.
Conclusions: Eplerenone inhibited the aggravation of cardiac inflammation and hypertensive cardiac remodeling, and thereby prevented progression of LV dysfunction in SHRs with large BPV. This suggests that the PAK1-MR pathway plays a role in cardiac inflammation and remodeling induced by large BPV superimposed on hypertension, independent of circulating aldosterone.
Details
- Title: Subtitle
- Blood Pressure Variability Activates Cardiac Mineralocorticoid Receptor and Induces Cardiac Remodeling in Hypertensive Rats
- Creators
- Suguru Yasuoka - Kurume UniversityHisashi Kai - Kurume UniversityHidemi Kajimoto - Kurume UniversityHiroshi Kudo - Kurume UniversityNarimasa Takayama - Kurume UniversityTakahiro Anegawa - Kurume UniversityMitsuhisa Koga - Kurume UniversityTakanobu Miyamoto - Kurume UniversityHiroharu Mifune - Kurume UniversityMasayoshi Kage - Kurume University HospitalYoshitaka Hirooka - Kyushu UniversityTsutomu Imaizumi - Kurume University
- Resource Type
- Journal article
- Publication Details
- Circulation journal : official journal of the Japanese Circulation Society, Vol.77(6), pp.1474-1481
- DOI
- 10.1253/circj.CJ-12-1253
- PMID
- 23470864
- NLM abbreviation
- Circ J
- ISSN
- 1346-9843
- eISSN
- 1347-4820
- Publisher
- Japanese Circulation Soc
- Number of pages
- 8
- Grant note
- Ishibashi Memorial foundation Ministry of Education, Science, Sports and Culture, Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Kimura Memorial Heart foundation Cardiovascular Research Institute
- Language
- English
- Date published
- 2013
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961114002771
Metrics
3 Record Views