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 platelet cytosolic calcium. Eight normal volunteers were given 0.8 mg fludrocortisone daily for 7 days (short protocol). Eight other normal volunteers ingested the drug for 6 weeks (long protocol). In the short protocol, fludrocortisone increased platelet cytosolic calcium and body weight by day 3, while BP was increased by day 7. In the long protocol, platelet cytosolic calcium was increased after 1 week, returned to basal values by 3 weeks and remained at that level for the rest of the study. Stimulation of the subjects' platelets ex vivo with thrombin and vasopressin led to a significant increase in intracellular free calcium concentration; however, fludrocortisone treatment did not alter the calcium response to either agonist. Fludrocortisone decreased serum potassium, plasma renin activity, plasma noradrenaline concentration and serum ionised calcium. These changes, as well as the BP increase, reverted to basal values when the drug was discontinued. We next incubated human platelets with fludrocortisone (1.4 nmol/l) and found a significant 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 cytosolic calcium and blood pressure are dissociated in that cytosolic calcium increases before the BP increase and later decreases to lower values, while the BP increase is sustained. Mineralocorticoid also has a direct effect on platelet cytosolic calcium in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)