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MOUSE STRAIN‐SPECIFIC DIFFERENCES IN CARDIAC METABOLIC ENZYME ACTIVITIES OBSERVED IN A MODEL OF ISOPROTERENOL‐INDUCED CARDIAC HYPERTROPHY
Author(s) -
Faulx Michael D,
Chandler Margaret P,
Zawaneh Michael S,
Stanley William C,
Hoit Brian D
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04531.x
Subject(s) - medicine , endocrinology , citrate synthase , muscle hypertrophy , enzyme , carnitine , metabolism , pyruvate dehydrogenase complex , catecholamine , enzyme assay , basal (medicine) , cardiac hypertrophy , chemistry , biology , biochemistry , insulin
SUMMARY1 Alterations in myocardial energy metabolism accompany pressure overload‐induced hypertrophy. We previously described a novel model of catecholamine‐induced hypertrophy in which A/J mice exhibit more robust cardiac hypertrophy than B6 mice. Accordingly, we assessed the influence of mouse strain on the activities of key myocardial metabolic enzymes and whether there are strain‐related metabolic adaptations to short‐term, high‐dose isoproterenol (ISO) administration. 2 Thirty‐nine male mice (19 A/J mice, 20 B6 mice), aged 12–15 weeks, were randomly assigned to receive either ISO (100 mg/kg, s.c.) or vehicle (sterile water) daily for 5 days. On Day 6, all hearts were excised, weighed, freeze clamped and assayed for pyruvate dehydrogenase (PDH), medium chain acyl‐CoA dehydrogenase, carnitine palmitoyl transferase I and citrate synthase activities. Plasma fatty acids (FA) were also measured. 3 The ISO‐treated A/J mice demonstrated greater percentage increases in gravimetric heart weight/bodyweight ratio than ISO‐treated B6 mice (24 vs 3%, respectively; P < 0.001). All enzyme activities were significantly greater in vehicle‐treated B6 mice than in A/J mice, illustrating a greater capacity for aerobic metabolism in B6 mice. Administration of ISO reduced PDHa (active form) activity in B6 mice by 47% ( P < 0.001), with no significant change seen in A/J mice. Free FA levels were not significantly different between groups; thus, the differences in PDHa were not due to changes in FA. 4 The basal activity of myocardial metabolic enzymes is greater in B6 mice than in A/J mice and ISO alters myocardial PDH activity in a mouse strain‐dependent manner. Compared with A/J mice, B6 mice demonstrate less ISO‐induced cardiac hypertrophy, but greater activity of key enzymes regulating FA and carbohydrate oxidation, which may protect against the development of hypertrophy. The metabolic adaptations associated with ISO‐induced hypertrophy differ from those reported with pressure overload hypertrophy.