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Beneficial effects of MET‐88 on left ventricular dysfunction and hypertrophy with volume overload in rats
Author(s) -
Nakano Motoko,
Kirimoto Tsukasa,
Asaka Naomasa,
Hayashi Yukio,
Kanno Tomohiro,
Miyake Hidekazu,
Matsuura Naosuke
Publication year - 1999
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1999.tb00356.x
Subject(s) - preload , medicine , captopril , cardiology , muscle hypertrophy , hemodynamics , shunt (medical) , heart failure , endocrinology , volume overload , left ventricular hypertrophy , blood pressure
— We examined the effects of MET‐88 on haemodynamics and cardiac hypertrophy in rats with an aortocaval shunt (A‐V shunt). On the day of surgery, an A‐V shunt was produced by using an 18‐gauge needle in Wistar rats as described by Garcia and Diebold. MET‐88 and captopril were orally administered to rats 1 week after surgery, and the administration was continued for 3 weeks. Four weeks after the surgery, A‐V shunt‐operated rats had biventricular hypertrophy and higher right atrial pressure (RAP) and left ventricular end‐diastolic pressure (LVEDP) than sham‐operated rats. Compared with untreated A‐V shunt rats, those treated with MET‐88 showed significant attenuation of the development of left ventricular (LV) hypertrophy and of the increased LVEDP. Captopril‐treated A‐V shunt rats also failed to show increases in LV weight and LVEDP. In in vitro studies, MET‐88 had no effect on renin and angiotensin‐converting enzyme (ACE) activities in the plasma of normal rats. These results suggest that MET‐88 improved LV hypertrophy and LV dysfunction in rats with an A‐V shunt. Furthermore, the data indicate that the beneficial effects of MET‐88 may be attributed to some pathway, not involving the renin‐angiotensin system, such as myocardial energy metabolism, venous return, etc. We conclude that MET‐88 may be a novel agent for the therapy of chronic heart failure.