Beneficial effects of MET-88 on left ventricular dysfunction and hypertrophy with volume overload in rats.
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.
Nakano
M
M
Pharmacology Research Laboratory, Taiho Pharmaceutical Co. Ltd., Tokushima, Japan.
Kirimoto
T
T
Asaka
N
N
Hayashi
Y
Y
Kanno
T
T
Miyake
H
H
Matsuura
N
N
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects*; D006332:Cardiomegaly / Q000517:prevention & control*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006321:Heart / Q000254:growth & development; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*
D002317:Cardiovascular Agents; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D007703:Peptidyl-Dipeptidase A; D012083:Renin