title: Perindopril effect on uncoupling protein and energy metabolism in failing rat hearts.
abstract: Uncoupling proteins, inner mitochondrial membrane proton transporters, are important for regulating myocardial energy efficiency. We investigated the effects of the ACE inhibitor perindopril on cardiac performance, myocardial energy efficiency, and uncoupling protein expression in an aortic regurgitation rat model. Twenty male Sprague-Dawley rats, in which aortic regurgitation was produced, were divided into untreated and perindopril-treated (5 mg x kg(-1) x d(-1)) rats. The treatments were initiated 3 days after operation. Ten control rats were sham-operated. Measurements of blood pressure and echocardiography were repeated before and 100 days after operation (endpoint). Left ventricular uncoupling protein-2 expression, creatine phosphate, and adenosine triphosphate were measured at endpoint. In perindopril-treated rats, systolic and diastolic blood pressure decreased after treatment (92+/-4/65+/-2 mm Hg). At endpoint, left ventricular end-diastolic dimension in untreated (10.7+/-0.2 mm) and treated rats (9.2+/-0.2 mm) was increased, and fractional shortening was reduced in untreated rats (28+/-1%) but did not change in treated rats (36+/-2%). Uncoupling protein-2 mRNA expression increased in untreated rats (3.7-fold) and was suppressed by perindopril (1.5-fold). The creatine phosphate was reduced in untreated rats (10.6+/-0.7 micro mol/g) but not in treated rats (15.9+/-2.0 micro mol/g). In the chronic stage of aortic regurgitation, perindopril improved cardiac performance and myocardial energy efficiency, in which the suppression of uncoupling protein-2 may play an important role.
authors.affiliation: Second Department of Internal Medicine, Kagawa Medical University, Kita, Kagawa, Japan. katsumz@kms.ac.jp
authors.forename: Kazushi
authors.initials: K
authors.lastname: Murakami
authors.forename: Katsufumi
authors.initials: K
authors.lastname: Mizushige
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noma
authors.forename: Teppei
authors.initials: T
authors.lastname: Tsuji
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D015150:Echocardiography, Doppler; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril / Q000494:pharmacology*; D010725:Phosphocreatine / Q000032:analysis; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071246:Uncoupling Protein 2
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D010725:Phosphocreatine; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D020913:Perindopril