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The induction of cardiac hypertrophy by catecholamines can be dissociated from their inotropic effect
P G Carlier1, R J Gilles, N S Smelten
1Département de Médecine, Université de Liège, Belgium.
Insights
Ornithine decarboxylase activity increases with cardiac hypertrophy, regulated by wall stress and adrenergic receptors. Catecholamines promote heart growth independently of pressure, influenced by calcium levels.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Cardiac hypertrophy involves early molecular changes.
- Ornithine decarboxylase (ODC) is key in polyamine synthesis.
- ODC activity may indicate early hypertrophic responses.
Purpose of the Study:
- To investigate ODC as an early marker for cardiac hypertrophy.
- To determine if ODC is regulated by ventricular wall stress and adrenergic receptors.
- To explore the role of catecholamines and calcium in ODC regulation.
Main Methods:
- Isovolumic perfused rat hearts model.
- In vitro assay of ornithine decarboxylase activity using 14C-ornithine decarboxylation.
- Administration of beta 2-adrenergic agonist (terbutaline).
- Manipulation of extracellular calcium levels.
- Induction of passive ventricular wall stress.
Main Results:
- Terbutaline increased ODC activity in both ventricles without altering cardiac performance.
- ODC stimulation by catecholamines, but not basal activity, depended on extracellular calcium.
- Increased ventricular wall stress elevated left ventricular ODC activity.
- ODC activity is independently regulated by wall stress and adrenergic receptors.
Conclusions:
- Ornithine decarboxylase is a sensitive marker for early cardiac hypertrophy.
- Catecholamines exert a pressure-independent trophic effect on the heart via ODC.
- Both mechanical stress and beta-adrenergic signaling influence ODC activity in cardiac hypertrophy.
Abstract:
In this study, ornithine decarboxylase, the first and rate-limiting enzyme of the polyamine pathway, was used as a marker of the very early stages of cardiac hypertrophy. Our data show that ornithine decarboxylase is independently regulated by ventricular wall stress and adrenergic receptors, and support the theory that catecholamines have a pressure-independent trophic effect. The infusion of beta 2-adrenergic agonist, terbutaline, at 10(-7) mol/l, did not affect the cardiac performance of isovolumic perfused rat hearts. Despite the lack of functional changes, ornithine decarboxylase activity, as assayed in vitro by 14C-ornithine decarboxylation, was markedly increased in both left and right ventricles. Further investigation showed that ornithine decarboxylase stimulation by catecholamines, unlike ornithine decarboxylase basal activity, was dependent on the extracellular calcium level. Furthermore, passive increases in ventricular wall stress in non-beating hearts also increased left ventricular ornithine decarboxylase activity.