[Prothrombotic aldosterone action--a new side of the hormone].
Recent studies have focused on a new wave of interest in aldosterone due mainly to its growing profile as a local messenger in pathology of the cardiovascular system, rather than its hormonal action. In the last few years strong evidence for a correlation between raised aldosterone level and haemostasis disturbances leading to increased risk of cardiovascular events has been provided. It has been demonstrated that aldosterone contributes to endothelial dysfunction, fibrinolytic disorders and oxidative stress augmentation. It was also shown that chronic aldosterone treatment results in enhanced experimental arterial thrombosis. Our study in a venous model of thrombosis in normotensive rats confirmed that even a short-lasting increase in aldosterone level intensified thrombus formation. One-hour aldosterone infusion shortened bleeding time; increased platelet adhesion to collagen; reduced tissue factor, thrombin activatable fibrinolysis inhibitor, and plasminogen activator inhibitor; and increased plasminogen activator plasma level. A fall in plasma nitric oxide metabolite concentration with a decrease in aortic nitric oxide synthase mRNA level was also observed. Moreover, aldosterone increased hydrogen peroxide and malonyl dialdehyde plasma concentration and augmented NADPH oxidase and superoxide dismutase aortic expression. Therefore, the mechanism of aldosterone prothrombotic action is multiple and involves primary haemostasis activation, procoagulative and antifibrinolytic action, NO bioavailability impairment and oxidative stress augmentation. The effects of aldosterone were not fully abolished by mineralocorticoid receptor blockade, suggesting the involvement of alternative mechanisms in the prothrombotic aldosterone action.
Samodzielna Pracownia Biofarmacji, Uniwersytet Medyczny, 15-222 Białystok. anagro@tlen.pl
Anna
A
Gromotowicz
Urszula
U
Osmólska
Maria
M
Mantur
Piotr
P
Szoka
Agnieszka
A
Zakrzeska
Janusz
J
Szemraj
Ewa
E
Chabielska
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D000077545:Eplerenone; D006487:Hemostasis / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D051381:Rats; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013927:Thrombosis
D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone