Chronic exercise induces pathological left ventricular hypertrophy in adrenaline-deficient mice

Abstract Adrenaline-deficient phenylethanolamine- N -methyltransferase-knockout mice (Pnmt-KO) have concentric heart remodeling and though their resting blood pressure is normal, it becomes higher during acute exercise. The aim of this study was to evaluate cardiac morphological, functional and molecular alterations after chronic exercise in adrenaline-deficient mice. Genotypes at the Pnmt locus were verified by polymerase chain reaction (PCR) of ear samples of Pnmt-KO and wild-type (WT) mice. These mice were submitted to chronic exercise training during 6weeks. Blood pressure was determined by a photoelectric pulse detector. Mice were anesthetized and cardiac morphology and function were evaluated by echocardiography and hemodynamics. IGF-1, IGF-1R, ANP and BNP mRNA were quantified by real-time PCR in left ventricle (LV) samples. Pnmt-KO mice showed increased systolic blood pressure compared with WT mice. A significant increase was found in LV mass, and LV posterior wall thickness in trained Pnmt-KO compared to trained WT mice, without significant differences in LV volumes. Acute β 1 -adrenergic stimulation with dobutamine increased systolic function indexes in WT mice, but not in Pnmt-KO mice. LV expression of IGF-1 and ANP was increased in trained Pnmt-KO mice when compared to trained WT mice. In conclusion, in response to chronic exercise adrenaline-deficient Pnmt-KO mice show concentric LV hypertrophy and impaired response to dobutamine, suggesting an initial stage of pathological cardiac hypertrophic remodeling. These results support the need for an efficient partial conversion of noradrenaline into adrenaline for prevention of blood pressure overshoot and thus pathological cardiac hypertrophic remodeling in chronic exercise.