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)