ELEVATED CYTOSOLIC CALCIUM OF ADIPOCYTES IN CHRONIC-RENAL-FAILURE

Chronic renal failure (CRF) is associated with increased calcium content of, and impaired lipase release from lipid cells. This has been attributed to a rise in the cytosolic calcium ([Ca2+]i) of these cells. However, data on [Ca2+]i of lipid cells in CRF and on the mechanisms responsible for such an abnormality are lacking. To study this issue we examined the [Ca2+]i and ATP content of lipid cells and V-max of Na+-K+-ATPase and Ca2+ ATPase of membrane preparation and Na+-Ca2+ exchange of membrane vesicles of adipocytes from normal rats, 6 week CRF, CRF normocalcemic parathyroidectomized (CRF-PTX) and CRF, and normal rats treated with verpamil (CRF-V), normal-V). [Ca2+]i in adipocytes of CRF rats was higher (199 +/- 8.5 nM) and ATP lower (2.9 +/- 0.31 nmol/10(6) cells) than in normal (120 +/- 4.3 nM; 5.7 +/- 0.27 nmol/10(6) cells), CRF-PTX (128 +/- 4.7 nM; 5.8 +/- 0.39 nmol/10(6) cells), normal-V (121 +/- 3.2 nM; 5.3 +/- 0.36 nmol/10(6) cells), CRF-V (123 +/- 7.4 nM; 5.5 +/- 0.30 mnol/10(6) cells). V-max Ca(2+)ATPase and the activity of Na+-K+-ATPase and of Na+-Ca2+ exchanger were reduced in CRF rats as compared to the other four groups of rats. The values in normal, CRF-PTX, CRF-V and normal-V rats were not different. These results indicate that: (1) in CRF, adipocytes are overloaded by calcium; (2) this abnormality is mediated by the secondary hyperthyroidism of CRF since PTX of CRF rats or interference with the action of PTH by a calcium channel blocker prevented these changes; and (3) the elevation in [Ca2+]i is due to both increased entry of calcium into adipocytes and a decreased extrusion out of these cells.