Effects of the mineralocorticoid fludrocortisone on fibrinolytic function in healthy subjects.
Recent evidence suggests that the renin-angiotensin-aldosterone system (RAAS) may participate in the regulation of fibrinolytic function. Angiotensin II (Ang II) is the primary candidate to mediate this inter-relationship, since this peptide is capable of stimulating plasminogen activator inhibitor-1 (PAI-1) in vitro and in vivo. It has been suggested that aldosterone may also modulate fibrinolysis, possibly by interacting with Ang II. The present study therefore investigates the effect of short-term treatment with the synthetic mineralocorticoid fludrocortisone (F) on fibrinolytic function. Ten healthy male volunteers, aged 25 to 30 years, on a constant intake of 160-180 mmol Na(+) and 60-80 mmol K(+), were studied on a control day (C1), after two days of oral administration of F (0.1 mg b.d.), and again three days after cessation of F (C2). F was associated with a marked decrease in plasma renin activity (PRA) from 0.91 +/- 0.45 ng ml(-1) h(-1) to 0.34 +/- 0.29 ng ml(-1) h(-1) (p=0.005), which returned to the baseline range at C2 (0.65 +/- 0.45 ng ml(-1) h(-1); p=0.032). The experimental protocol was not associated with significant changes in the activity or antigen concentration of tissue plasminogen activator (t-PA). PAI-1 exhibited a circadian rhythm with highest values at 0800 hours (41.8 +/- 9.1 ng/ml), decreasing by 1230 hours (22.6 +/- 5.9 ng/ml), with a further decrease at 1630 hours (12.3 +/- 3.1 ng/ml). At all three time points, PAI-1 remained unchanged by the mineralocorticoid. Our results therefore do not support a major mineralocorticoid effect on PAI-1. However, our study does not exclude a modulatory role of F, since unchanged PAI-1 could be observed in spite of a marked suppression of the RAAS.
Lottermoser
K
K
Universitats-Poliklinik Bonn, Bonn, 53111, Germany.
Hertfelder
H J
HJ
Wehling
M
M
Schiermeyer
B
B
Vetter
H
H
Düsing
R
R
D000328:Adult; D002940:Circadian Rhythm; D005342:Fibrinolysis / Q000187:drug effects*; D005438:Fludrocortisone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology*; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012016:Reference Values; D012083:Renin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood
D008901:Mineralocorticoids; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D012083:Renin; D005438:Fludrocortisone