ALTERATION OF CARDIAC ENERGY-STATE DURING DEVELOPMENT OF HYPERTENSIONIN RATS OF THE LYON STRAIN - A P-31-NMR STUDY ON THE ISOLATED RAT-HEART

The effect of different chronic blood pressure levels on cardiac energ y metabolism was studied by P-31-NMR spectroscopy in perfused hearts f rom the Lyon strains of hypertensive (LH), normotensive (LN) and hypot ensive (LL) rats at the ages of 12 and 21 weeks. The in vivo assessmen t of haemodynamic parameters measured at 21 weeks in anaesthetized rat s with an ultraminiature catheter pressure transducer confirmed that l eft ventricular systolic pressure and mean aortic pressure were signif icantly greater (+25%) in LH rats than in LN and LL rats. In the LL an imals, left ventricular systolic pressure was slightly reduced (-10%) and cardiac contractility (estimated by LV dP/dt(max)) showed a 24% de creased compared to normotensive animals. The energy state of the card iomyocytes was characterized at different work levels of isolated rat hearts, by determining the concentration of the free phosphorylated co mpounds at each work level. Changes in workload were induced by varyin g the calcium concentration in the perfusion fluid. Increasing extrace llular calcium concentration resulted in a similar increase in left ve ntricular developed pressure (LVDP) in all groups studied. Intracellul ar pH was not influenced by either the age of the animals or the level of cardiac work, in the three groups of animals. ATP content of the L N and LL rats remained constant during the whole perfusion period whil e the 12 week-old LH rats showed a decreased ATP content with increasi ng cardiac work. In the older LH rats, ATP content was decreased at th e highest work level (corresponding to 2 mm calcium). In response to t he increase in work, phosphocreatine (PCr) content diminished and inor ganic phosphate (Pi) content increased in both LN, LH and LL animals. PCr degradation and Pi accumulation were higher in the LH rats and les s in LL rats compared to the LN. These changes were more important in the younger than in the older hypertensive animals. The relationship b etween LVDP and [Pi]/[PCr] indicates that oxidative metabolism is maxi mally activated in the young hypertensive rats and suggests that this maximal activation represents an adaptative phase to the increase in b lood pressure. Since the difference between the metabolic pattern of t he 21 week-old LH rats and age-matched LN rats was less pronounced, it is likely that a compensatory stage has been reached at that age.