EFFECT OF EXOGENOUS MINERALOCORTICOID ON PLATELET CYTOSOLIC CALCIUM IN NORMAL HUMANS

We tested the hypothesis that the fludrocortisone in doses sufficient to elevate blood pressure (BP) in normal subjects would increase plate let cytosolic calcium. Eight normal volunteers were given 0.8 mg fludr ocortisone daily for 7 days (short protocol). Eight other normal volun teers ingested the drug for 6 weeks (long protocol). In the short prot ocol, fludrocortisone increased platelet cytosolic calcium and body we ight by day 3, while BP was increased by day 7. In the long protocol, platelet cytosolic calcium was increased after 1 week, returned to bas al values by 3 weeks and remained at that level for the rest of the st udy. Stimulation of the subjects' platelets ex vivo with thrombin and vasopressin led to a significant increase in intracellular free calciu m concentration; however, fludrocortisone treatment did not alter the calcium response to either agonist. Fludrocortisone decreased serum po tassium, plasma renin activity, plasma noradrenaline concentration and serum ionised calcium. These changes, as well as the BP increase, rev erted to basal values when the drug was discontinued. We next incubate d human platelets with fludrocortisone (1.4 nmol/l) and found a signif icant increase in cytosolic calcium by 30 min. The data suggest that a blood pressure-raising dose of mineralocorticoid leads to a transient (days to weeks) increase in platelet cytosolic calcium. Platelet cyto solic calcium and blood pressure are dissociated in that cytosolic cal cium increases before the BP increase and later decreases to lower val ues, while the BP increase is sustained. Mineralocorticoid also has a direct effect on platelet cytosolic calcium in vitro. Whether the effe ct on platelet cytosolic calcium in vivo is direct, is mediated by a v olume-associated servo mechanism, or by other means cannot be discerne d from these data.