Abnormal transport of inorganic phosphate in left ventricular mitochondria from spontaneously hypertensive rats.

INTRODUCTION: The aim of this study was to investigate the kinetic properties of inorganic phosphate (Pi) translocator in intact mitochondria isolated from the hypertrophied left ventricular tissue of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at the ages of 5 and 24 weeks, before and after the development of hypertension. METHODS: The dependence of the Pi uptake rate on substrate concentration was measured in both absence and presence of mersalyl by spectroscopic techniques. RESULTS: Saturation characteristics were found (Km 250.0 +/- 25.0 and 15.0 +/- 1.5 microM for 5- and 24-week-old SHR, and 300.0 +/- 30.0 and 40.0 +/- 4.5 microM for WKY rat mitochondria, respectively, p < 0.05; Vmax 1.2 +/- 0.16 and 0.1 +/- 0.01 delta A/min x mg mitochondrial proteins for 5- and 24-week-old SHR, and 4.1 +/- 0.39 and 1.4 +/- 0.12 delta A/min x mg mitochondrial proteins for 5- and 24-week-old WKY rats, respectively, p < 0.05). When Pi carrier activity was measured using concentrations which are assumed to be in the cytosol under physiological conditions, Pi carrier velocity was 1.1 and 0.1 in SHR and 4.6 and 1.4 delta A/min x mg mitochondrial proteins in WKY, at 5 and 24 weeks, respectively. CONCLUSIONS: The significant decrease in the activity of the Pi carrier could imply that pressure overload is critical in SHR. Nevertheless, as decreased activity was found in SHR also at an early age when animals do not show stable increased blood pressure levels, we suggest that other factors might contribute to the abnormalities of Pi transport in mitochondria. An altered gene expression possibly related to a primary defect in this strain or, alternatively, to an abnormal regulation of protein synthesis might be proposed as additional factors affecting Pi carrier activity. The results of this study, together with previous data of the literature showing abnormalities in energy production mechanisms, allow us to hypothesize a profound rearrangement of energy metabolism at the mitochondrial level in this model of left ventricular hypertrophy and hypertension.