|
Sign In to gain access to subscriptions and/or personal tools.
|
Effects of the mineralocorticoid fludrocortisone on fibrinolytic function in healthy subjects
Katja Lottermoser
Medizinische Universitäts-Poliklinik Bonn, Germany
Hans-Jörg Hertfelder
Institut für Experimentelle Hämatologie und Transfusionsmedizin Bonn, Germany
Martin Wehling
Institut für klinische Pharmakologie Mannheim, Germany
Beate Schiermeyer
Medizinische Universitäts-Poliklinik Bonn, Germany
Hans Vetter
Medizinische Universitäts-Poliklinik Bonn, Germany
Rainer Düsing
Medizinische Universitäts-Poliklinik Bonn, Germany, duesing@ uni-bonn.de
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.
Key Words: mineralocorticoid • fludrocortisone • angiotensin II • fibrinolysis • plasma renin activity • plasminogen activator inhibitor-1 • tissue plasminogen activator
References
- Brunner HR, Laragh JH, Baer L. et al. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972;286:441-9.[Web of Science][Medline]
[Order article via Infotrieve]
- Alderman MH, Madhavan S., Ooi WL, Cohen H., Sealey JE, Laragh JH Association of renin-sodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med 1991;324:1098-104.[Abstract]
- Lottermoser K., Vetter H., Düsing R. Blood pressure-independent atherogenic and thromboembolic mechanisms of the renin-angiotensin-aldosterone system. J Clin Basic Cardiol (in press).
- Gray RP, Yudkins JS, Patterson DL Plasminogen activator inhibitor: a risk factor of myocardial infarction in diabetic patients. Br Heart J 1993;69:228-32.[Abstract/Free Full Text]
- Scarabin PY, Aillaud MF, Amouyel P. et al. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction-the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost 1998;80:749-56.[Web of Science][Medline]
[Order article via Infotrieve]
- Thogersen AM, Jansson JH, Boman K. et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 1998;98:2241-7.[Abstract/Free Full Text]
- Vaughan DE, Lazos SA,Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells.A potential link between the renin-angiotensin system and thrombosis. J Clin Invest 1995;95:995-1001.[Web of Science][Medline]
[Order article via Infotrieve]
- Nishimura H., Tsuji H., Masuda H. et al. Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue-type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells. Thromb Haemost 1997;77;1189-95.[Web of Science][Medline]
[Order article via Infotrieve]
- Hamdan AD, Quist WC, Gagne JB et al. Angiotensin-converting enzyme inhibition suppresses plasminogen activator inhibitor-1 expression in the neointima of balloon-injured rat aorta. Circulation 1996;93:1073-8.[Abstract/Free Full Text]
- Ridker PM, Gaboury CL, Conlin PR, Seely EW,Williams GH, Vaughan DE Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function.Circulation 1993;87:1969-73.[Abstract/Free Full Text]
- Brown NJ, Agirbasli MA, Williams GH, Litchfield WR, Vaughan DE Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. Hypertension 1998;32:965-71.[Abstract/Free Full Text]
- Brown NJ,Agirbasli M.,Vaughan DE Comparative effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on plasma fibrinolytic balance in humans. Hypertension 1999;34:285-90.[Abstract/Free Full Text]
- Pedersen OD, Gram J., Bagger H., Keller N., Jespersen J. Regulation of tissue-type plasminogen activator-mediated fibrinolysis by plasminogen activator inhibitor type-1 in patients with ischemic heart disease: possible unfavourable effect of diuretics. CoronaryArtery Disease 1994;5:617-23.
- Lottermoser K., Weisser B., Hertfelder H-J., Wöstmann B., Vetter H., Düsing R. Antihypertensive drug treatment and fibrinolytic function. AJH 1998;11:378-84.[Medline]
[Order article via Infotrieve]
- Goodfield NE, Newby DE, Ludlam CA, Flapan AD Effects of acute angiotensin II type 1 receptor antagonism and angiotensin-converting enzyme inhibition on plasma fibrinolytic parameters in patients with heart failure. Circulation 1999;99:2983-5.[Abstract/Free Full Text]
- Pitt B., Zannad F., Remme WJ et al. for the RALES Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-17.[Abstract/Free Full Text]
- Brilla CG, Maisch B. Regulation of the structural remodeling of the myocardium: from hypertrophy to heart failure. Europ Heart J 1994;15(Suppl D):45-52.[Abstract/Free Full Text]
- Brilla CG, Maisch B., Zhou G., Weber KT Hormonal regulation of cardiac fibroblast function. Eur Heart J 1995;16(Suppl C):45-50.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Brown NJ, Kim KS, Chen YQ et al. Synergistic effect of adrenal steroids and angiotensin II on plasminogen activator inhibitor-1 production. J Clin Endocrinol Metab 2000; 85(1):336-44.[Abstract/Free Full Text]
- Verheijen JH, Chang GTG, Kluft C. Evidence for the occurence of a fast acting inhibitor of tissue-type plasminogen activator in plasma. Thromb Haemost 1984;51:392-495.[Medline]
[Order article via Infotrieve]
- Haber E., KoernerT, Page LB et al. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol 1969;29:1349-55.[Abstract/Free Full Text]
- Lottermoser K., Hertfelder H-J., Vetter H., Düsing R. Fibrinolytic function in diuretic-induced volumen depletion. Am J Hypertens 13:359-63.
- Nakamura S., Nakamura I., Nishimura H., Vaughan D., Fogo A. Plasminogen activator inhibitor-1 (PAI-1) is induced directly by angiotensin type 1 receptor in vivo. J Am Soc Nephrol 1998; 9: 523 A.
- Erdem Y., Usalan C., Haznedaroglu IC et al. Effects of angiotensin-converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension. Am J Hypertens 1999;12:1071-6.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Vaughan DE, Lazos SA,Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. J Clin Invest 1995;95:995-1001.[Web of Science][Medline]
[Order article via Infotrieve]
- Kerins DM, Hao Q., Vaughan DE Angiotensin induction of PAI-expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest 1995;96: 2515-520.[Web of Science][Medline]
[Order article via Infotrieve]
- Daley WL, Plavin S., Vaughan DE The induction of plasminogen activator inhibitor-1 by the hexapeptide (3-8) fragment of the renin angiotensin system is not pressor dependent. Circulation 1998;98 (Suppl.): 1519.
- Verrey F. Early aldosterone action: toward filling the gap between transcription and transport. Am J Physiol 1999; 277(3Pt2):F319-327.[Web of Science][Medline]
[Order article via Infotrieve]
- Stewart PM Mineralocorticoid hypertension. Lancet 1999; 353:1341-7.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Funder JW Aldosterone, salt and cardiac fibrosis. Clin Exp Hypertens 1997;19:885-99.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wehling M. Specific, nongenomic steroid action.Ann Rev Physiol 1997;59:365-93.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Christ M., Wehling M. Cardiovascular steroid actions: swift swallows or sluggish snails? Cardiovasc Res 1998;40:34-44. 33. Hollenberg NK, Chenitz WR, Adams DF, Williams GH Reciprocal influence of salt intake on adrenal glomerulosa and renal vascular responses to angiotensin II in normal man. J Clin Invest 1974;54:34-42.[Web of Science][Medline]
[Order article via Infotrieve]
- Oelkers W., Brown JJ, Fraser R., Leber AF, Morton JJ, Robertson JI Sensitization of the adrenal cortex to angiotensin II in sodium-deplete man. Circ Res 1974;40:69-77.[Medline]
[Order article via Infotrieve]
- Ullian ME, Fine JJ Mechanisms of enhanced angiotensin II-stimulated signal transduction in vascular smooth muscle by aldosterone. J Cell Physiol 1994;161(2):201-8.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 4,
357-360 (2000)
DOI: 10.3317/jraas.2000.066
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
|
|
