Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against beta1-adrenoceptor.
We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1-peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor.
Matsui
S
S
Department of Cardiology, Kanazawa Medical University, Ishikawa, Japan. matsui@kanazawa-med.ac.jp
Fu
M
M
Hayase
M
M
Katsuda
T
T
Yamaguchi
N
N
Teraoka
K
K
Kurihara
T
T
Takekoshi
N
N
Wakabayashi
H
H
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015551:Autoimmunity; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D017706:Lisinopril / Q000097:blood / Q000627:therapeutic use*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D018342:Receptors, Adrenergic, beta-1; D017706:Lisinopril