ISSN:
1432-1440
Keywords:
Cyclosporine
;
Calcium
;
Na-KATPase
;
Vascular smooth muscle
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The effect of cyclosporine A in enhancing vasconstrictor-induced calcium (Ca2+) mobilization in vascular smooth muscle cells may contribute to important side effects in cyclosporine therapy such as hypertension and nephrotoxicity. As we have previously shown, cyclosporine A stimulates transmembrane Ca2+ influx. Since Ca2+ efflux was not affected by cyclosporine A, we concluded that cyclosporine augments angiotensin II induced Ca2+ mobilization in vascular smooth muscle cells by an increased amount of Ca2+ in angiotensin II sensitive intracellular Ca2+ stores. The present study was therefore designed to examine the effect of cyclosporine A on cellular calcium content and on membrane calcium transport mechanisms. An important mechanism of Ca2+ extrusion from the cell is the Na-Ca exchanger. Its activity is closely related with that of the Na-ATPase. By increasing cellular sodium concentration the blockade of Na-ATPase would in turn activate cellular calcium uptake bx the Na-Ca exchanger. Therefore, we hypothesized that cyclosporine A might exert its effects in the same manner as a circulating Na-ATPase inhibitor. Total cell calcium was measured by atomic absorption and activity of Na-ATPase was estimated by an assay measuring phosphate production. Preincubation of the cells with cyclosporine (10 μg/ml) for 15 min increased total cell calcium from 31.4 ± 5.0 to 46.5 ± 5.3 nmol/mg protein (P 〈 0.05). Activity of Na-ATPase was not affected by cyclosporine A (3.9 ± 0.2 vs. 4.3 ± 0.2 μol Pi h−1 mg−1 protein). Therefore, cyclosporine A induced Ca2+ influx is not mediated by an inhibition of the Na-ATPase. Cyclosporine-stimulated accumulation of cellular calcium may be mediated, for example, by opening of calcium channels in the plasma membrane. Increased Ca2+ mobilization in the presence of cyclosporine A may be due to an increased amount of Ca2+ avaible from intracellular Ca2+ stores. These results are of substantial significance for understanding the pathophysiological mechanisms of cyclosporine A induced vasoconstriction.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00577742
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