Effect of ecadotril, a neutral endopeptidase inhibitor, on myocardial hypertrophy in the rat aortic insufficiency model.
Cardiac hypertrophy develops to compensate for hemodynamic overload of the myocardium. However, cardiac hypertrophy itself poses a serious risk to patients with heart failure. Whether natriuretic peptides enhanced by ecadotril, a neutral endopeptidase inhibitor, suppress the increase of left ventricular mass in the rat aortic insufficiency model was investigated. Ecadotril suppressed the increase of the left ventricular mass without affecting blood pressure (710.9 +/- 15.6 mg in the group treated with ecadotril and 865.0 +/- 27.3 mg in the control group, P < 0.01). Although the increase of atrial natriuretic peptide in the left ventricle was trivial and did not reach statistical significance (406.5 +/- 62.2 pg/mg in the ecadotril-treated group versus 269.8 +/- 35.7 pg/mg in the control group), urinary cGMP excretion was greater in the group given ecadotril than in the control group (10.6 +/- 2.5 pmol/mL and 1.7 +/- 0.6 pmol/mL, respectively, P < 0.01). Plasma angiotensin II concentration also decreased in the group treated with ecadotril compared with the control group (116.6 +/- 25.4 pg/mL versus 358.7 +/- 98.7 pg/mL, P < 0.05). In conclusion, ecadotril suppressed the increase of left ventricular mass in the overloaded heart. In ecadotril-treated rats, cGMP synthesis was augmented and angiotensin II concentration was reduced.
Kimura
M
M
Department of Clinical Pharmacology and Pharmacology, Hamamatsu University School of Medicine, Japan. kimu01@akiha.hama-med.ac.jp
Umemura
K
K
Ohashi
K
K
Nakashima
M
M
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001018:Aortic Diseases / Q000097:blood / Q000150:complications* / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D004195:Disease Models, Animal; D006157:Guanosine Monophosphate / Q000652:urine; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology
D011480:Protease Inhibitors; D000804:Angiotensin II; C049331:racecadotril; D006157:Guanosine Monophosphate; D015244:Thiorphan