title: Angiotensin II type 1-receptor antagonist candesartan cilexitil prevents left ventricular dysfunction in myocardial infarcted rats.
abstract: The purpose of this study was to analyze the effect of the angiotensin II type 1-receptor antagonist candesartan cilexitil on left ventricular systolic and diastolic function and mRNA expression of contractile proteins, collagen, and Ca2+ handling protein in myocardial-infarcted rats. After myocardial infarction, the animals were randomly assigned to candesartan cilexitil-treated or untreated groups (MI). We performed Doppler-echocardiographic examination and measured the hemodynamics at four and twelve weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. At four weeks in MI, left ventricular end-diastolic dimension increased (Control, 6.2+/-0.6 mm; MI, 8.7+/-0.6 mm; P < 0.01), fractional shortening decreased (Control, 41+/-5%; MI, 16+/-3%; P < 0.01) and E wave deceleration rate increased (Control, 14.3+/-2.0 m/sec2; MI, 23.3+/-2.3 m/sec2; P < 0.01). Candesartan cilexitil significantly prevented these changes. The mRNA expressions of beta-myosin heavy chain, alpha-skeletal actin, atrial natriuretic peptide, and collagens I and III in the non-infarcted left ventricle and right ventricle were increased at four weeks and were significantly suppressed by treatment with candesartan cilexitil. At four weeks, Na+-Ca2+ exchanger mRNA expression was increased, and candesartan cilexitil suppressed this increase. At twelve weeks, sarcoplasmic reticulum Ca2+-ATPase mRNA expression in the infarcted region including the adjacent non-infarcted left ventricle and right ventricle were decreased and candesartan cilexitil restored it to the control level. Candesartan cilexitil prevented the systolic and diastolic dysfunction and abnormal cardiac mRNA expression in myocardial-infarcted rats.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hanatani
authors.forename: M
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Omura
authors.forename: H
authors.initials: H
authors.lastname: Iwao
authors.forename: J
authors.initials: J
authors.lastname: Yoshikawa
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000187:drug effects / Q000235:genetics; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000187:drug effects / Q000235:genetics; D003285:Contractile Proteins / Q000187:drug effects / Q000235:genetics; D004452:Echocardiography; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000235:genetics; D013777:Tetrazoles; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003285:Contractile Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019831:Sodium-Calcium Exchanger; D013777:Tetrazoles; D009320:Atrial Natriuretic Factor; D003094:Collagen; D000252:Calcium-Transporting ATPases; C077793:candesartan cilexetil