Adaptation to hypoxia alters energy metabolism in rat heart

The present study characterized metabolic changes in the heart associated w ith long-term exposure to hypoxia, a potent stimulus for pulmonary hyperten sion and right ventricular hypertrophy. When anesthetized rats adapted to c hronic hypoxia spontaneously respired room air, their mean right intraventr icular peak systolic pressure (RVSP) was twice that in normal control anima ls with the same arterial Po-2. RVSP was linearly related to right ventricu lar mass (r = 0.78). Oxidative capacity (O-2 consumption) of homogenates of right and left ventricles from both groups of rats was measured with one o f the following substrate: pyruvate, glutamate, acetate, and palmitoyl-L-ca rnitine. Oxidation of all substrates was significantly greater in the left than in the right ventricle in normal rats but not in hypoxia-adapted anima ls, where it was the same, within the experimental error. O-2 consumption b y the left ventricle was greater in control than in experimental rats, but right ventricular O-2 consumption was similar in the two groups. Maximal re action velocity of cytochrome-e oxidase was about the same in the two ventr icles, and there were no significant differences between control and hypoxi a-adapted animals. HPLC analyses showed significantly higher aspartate leve ls and aspartate-to glutamate concentration ratios in both ventricles of hy poxic rats than in corresponding tissues from controls, indicative of a dec reased flux through the malate-aspartate shuttle under conditions of O-2 li mitation. Myocardial glutamine levels were lower in hypoxic rats, and gluta mine-to-glutamate concentration ratios decreased, although primarily in the pressure-overloaded right ventricle. These findings indicate that normal e nergy metabolism in the left ventricle differs from that in the right and t hat the differences, particularly those of amino acid metabolism, are marke dly influenced by chronic exposure to hypoxia.