Adaptive changes in cardiac myosin heavy chain and creatine kinase isozymic profiles in rats native of altitude

Abstract

The developmental changes in the myosin heavy chain (MHC) profile, creatine kinase (CK) and lactate dehydrogenase (LDH) activities and isozyme expression occurring in heart were examined in rats born and living at altitude (La Paz, Bolivia, 3700 m, H(LP)) for 16 generations. We hypothesized that H(LP) rats respond differently to hypoxia than rats born and living at sea level, and secondarily exposed to altitude during 3 weeks (H(3W)). The cardiac expression of MHC, CK and LDH was studied in left (LV) and right ventricle (RV) of H(LP) animals 1, 2, 3, 4 and 18 weeks after birth, and compared with control normoxic (C groups) and H(3W) animals. Rats secondarily exposed to hypoxia showed a lower alpha-MHC content than C or H(LP) rats in both LV and RV, 3 weeks after birth (P < 0.05), consistent with a delay in the maturation of the heart contractile phenotype. A global increase in the total CK activity was observed in the LV of H(3W) animals in comparison with C rats (P < 0.05), while no change was reported in H(LP) animals. In both ventricles, M-LDH activity was higher in H(3W) than in H(LP) and C rats (P < 0.05). The relative amount of alpha-MHC decreased by 20% in RV of 18-week-old H(LP) and H(3W) rats in comparison with C animals, consistent with the hypoxia-induced ventricular enlargement (P < 0.01). An increased activity of the foetal B-CK subunit was observed in both LV and RV of H(3W) rats in comparison with H(LP) and C animals (P < 0.05). This study demonstrates that rats native and living at altitude for several generations present some features relevant to genetic selection to altitude.