Decreased ATP-synthesis ability of liver mitochondria in spontaneously hypertensive rats (SHR): Role of calcium overload of the mitochondria

It has been shown previously, that a decrease of ATP amount and changed balance of the other macroergic phosphates are observed in different tissues of spontaneously hypertensive rats (SHR) compared with the normotensive controls (WKY). The aim of the present study was to assess the ability of SHR liver isolated mitochondria to synthesize ATP and to clarify its dependence on extramitochondrial calcium concentration. Macroergic phosphate concentrations were measured by high performance liquid chromatography (HPLC). The present work shows for the first time, that SHR liver mitochondria initially differ from WKY ones by decreased (by 30%) ATP synthesis rate. Respiratory control coefficient and phosphorylation rate in SHR and WKY mitochondria change in different manner when extramitochondrial calcium concentration increases from 0 to 50 muM. When calcium concentration is increased up to 50 muM both parameters in WKY mitochondria are about one half compared with the condition when the medium does not contain calcium. In the conditions, when the medium contains 50 muM of calcium, complete uncoupling of oxidation and phosphorylation in SHR mitochondria is observed. Thus the decrease of ATP synthesis rate in SHR mitochondria in conjunction With reduced tolerance to calcium overload (by respiratory control coefficient and :phosphorylation rate) in comparison with WKY may be considered as the main cause of cell energy deficiency, observed in experimental variant of primary arterial hypertension.