Premium
Hypercholesterolaemia exacerbates ventricular remodelling after myocardial infarction in the rat: role of angiotensin II type 1 receptors
Author(s) -
Mączewski M,
Mączewska J,
Duda M
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.218
Subject(s) - losartan , medicine , atorvastatin , angiotensin ii , angiotensin ii receptor type 1 , endocrinology , myocardial infarction , downregulation and upregulation , cardiology , ventricular remodeling , renin–angiotensin system , receptor , heart failure , chemistry , blood pressure , biochemistry , gene
Background and purpose: Diet‐induced hypercholesterolaemia exacerbates post‐myocardial infarction (MI) ventricular remodelling and heart failure, but the mechanism of this phenomenon remains unknown. This study examined whether worsening of post‐MI ventricular remodelling induced by dietary hypercholesterolaemia was related to upregulation of angiotensin II type 1 (AT 1 ) receptor in the rat heart. Experimental approach: MI was induced surgically in rats fed normal or high cholesterol diet. Both groups of rats were then assigned to control, atorvastatin, losartan or atorvastatin+losartan‐treated subgroups and followed for 8 weeks. Left ventricular (LV) function was assessed with echocardiography. In isolated hearts, LV pressures were measured with a latex balloon and a tip catheter. AT 1 ‐receptor density was assessed in LV membranes with radioligand‐binding assays. Key results: High cholesterol diet exacerbated LV dilation and dysfunction in post‐MI hearts. Atorvastatin or losartan prevented these hypercholesterolaemia‐induced effects, whereas their combination was not more effective than each drug alone. AT 1 receptors were upregulated 8 weeks after MI, this was further increased by hypercholesterolaemia and restored to baseline levels by atorvastatin. Conclusions and implications: Hypercholesterolaemia exacerbated LV remodelling and dysfunction in post‐MI rat hearts and upregulated cardiac AT 1 receptors. All these effects were effectively prevented by atorvastatin. Thus, the pleiotropic statin effects may include interference with the renin‐angiotensin system through downregulation of AT 1 receptors. British Journal of Pharmacology (2008) 154 , 1640–1648; doi: 10.1038/bjp.2008.218 ; published online 9 June 2008