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Effect of MET‐88, a γ‐butyrobetaine hydroxylase inhibitor, on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart
Author(s) -
Akahira M,
Hara A,
Abiko Y
Publication year - 1997
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.1472-8206.1997.tb00849.x
Subject(s) - hydrogen peroxide , propionate , endocrinology , medicine , chemistry , metabolism , heart rate , blood pressure , biochemistry
Summary— The effect of MET‐88 (3‐(2,2,2‐trimethylhydrazinium) propionate dihydrate), a γ‐butyrobetaine (γ‐BB) hydroxylase inhibitor, on the hydrogen peroxide (H 2 O 2 )‐induced mechanical and metabolic derangements was studied in the isolated rat heart, which was perfused aerobically by the Langendorff s technique at a constant flow rate and driven electrically. In the first series of experiments, MET‐88 (100 mg/kg/d) was orally administered to rats for 10 days prior to isolation of the heart. In the second series of experiments, MET‐88 or γ‐BB was directly infused to the isolated perfused heart. In both series of experiments, H 2 O 2 (600 μM) decreased the left ventricular developed pressure (mechanical dysfunction) and the tissue levels of high‐energy phosphates (metabolic derangement). In the first series of experiments, oral pretreatment with MET‐88 attenuated the H 2 O 2 ‐induced metabolic derangement with a marked increase in the myocardial level of γ‐BB, while it did not attenuate the H 2 O 2 ‐induced mechanical dysfunction. In the second series of experiments, MET‐88 (1 mM) did not attenuate the H 2 O 2 ‐induced metabolic derangement, whereas γ‐BB (500 μM or 1 mM) attenuated it. Nevertheless, γ‐BB did not modify the energy metabolism of H 2 O 2 ‐untreated heart (normal heart). These results suggest that oral pretreatment with MET‐88 protects the energy metabolism against the H 2 O 2 ‐induced derangement and that the beneficial effect of the oral pretreatment with MET‐88 may be mediated by γ‐BB that has accumulated in the myocardium because of inhibition of γ‐BB hydroxylase.