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Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy
Author(s) -
Watanabe Kenichi,
Ohta Yoshimi,
Nakazawa Mikio,
Higuchi Hiroshi,
Hasegawa Go,
Naito Makoto,
Fuse Koichi,
Ito Masahiro,
Hirono Satoru,
Tanabe Naohito,
Hanawa Haruo,
Kato Kiminori,
Kodama Makoto,
Aizawa Yoshifusa
Publication year - 2000
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/sj.bjp.0703450
Subject(s) - medicine , carvedilol , preload , dilated cardiomyopathy , heart failure , blood pressure , heart rate , myocarditis , cardiology , ventricular pressure , central venous pressure , cardiomyopathy , hemodynamics , endocrinology
The cardioprotective properties of carvedilol (a vasodilating β‐adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty‐eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg −1 day −1 (Group‐C2, n =10) or 20 mg kg −1 day −1 (Group‐C20, n =10) of carvedilol, or vehicle (0.5% methylcellulose, Group‐V, n =12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat α‐atrial natriuretic peptide (r‐ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end‐diastolic pressure (LVEDP), ±dP dt −1 and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group‐N, n =10). Two out of 12 (17%) rats in Group‐V died from day 28 to day 42 after immunization. No rat died in Groups‐C2, ‐C20 and ‐N. Although the CVP, mean BP, LVP and ±dP dt −1 did not differ among the three groups, the HW, HR and r‐ANP in Group‐C2 (1.14±0.03, 339±16 and 135±31) and Group‐C20 (1.23±0.04, 305±8 and 156±24) were significantly lower than those in Group‐V (1.36±0.04 g, 389±9 beats min −1 and 375±31 pg ml −1 , respectively). The LVEDP in Group‐C2 was significantly lower than that in Group‐V (7.4±1.4 and 12.2±1.2 mmHg, respectively, P <0.05). The area of myocardial fibrosis in Group‐C2 was smaller than that in Group‐V (12±1 and 31±2%, P <0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.British Journal of Pharmacology (2000) 130 , 1489–1495; doi: 10.1038/sj.bjp.0703450