RESUMEN

INTRODUCTION: We investigated the role of primary haemostasis, fibrinolysis, nitric oxide (NO) and oxidative stress as well as mineralocorticoid receptors (MR) in acute aldosterone prothrombotic action. MATERIALS AND METHODS: Venous thrombosis was induced by stasis in Wistar rats. Aldosterone (ALDO; 10, 30, 100 µg/kg/h) was infused for 1 h. Eplerenone (EPL; 100 mg/kg, p.o.), a selective MR antagonist, was administered before ALDO infusion. Bleeding time (BT) and platelet adhesion to collagen were evaluated. The expression of nitric oxide synthase (NOS), NADPH oxidase, superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) was measured. NO, malonyl dialdehyde (MDA) and hydrogen peroxide (H(2)O(2)) plasma levels were assayed. RESULTS: Significant enhancement of venous thrombosis was observed after ALDO infusion. ALDO shortened BT and increased platelet adhesion. Marked increases were observed in PAI-1, NADPH oxidase and SOD mRNA levels. MDA and H(2)O(2) levels were augmented in ALDO-treated groups, and NOS expression and NO level were decreased. EPL reduced ALDO effects on thrombus formation, primary haemostasis, PAI-1 expression and MDA level. CONCLUSION: Short-term ALDO infusion enhances experimental venous thrombosis in the mechanism involving primary haemostasis, fibrinolysis, NO and oxidative stress-dependent pathways. The MR antagonist only partially diminished the ALDO effects, suggesting the involvement of additional mechanisms.

Asunto(s)

Aldosterona/metabolismo , Trombosis/patología , Aldosterona/sangre , Animales , Aorta/efectos de los fármacos , Aorta/enzimología , Aorta/patología , Disponibilidad Biológica , Tiempo de Sangría , Hemodinámica/efectos de los fármacos , Hemostasis , Masculino , Antagonistas de Receptores de Mineralocorticoides , Óxido Nítrico/sangre , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Inhibidor 1 de Activador Plasminogénico/metabolismo , Adhesividad Plaquetaria/efectos de los fármacos , Potasio/orina , Ratas , Ratas Wistar , Receptores de Mineralocorticoides/metabolismo , Trombosis/sangre , Trombosis/fisiopatología , Trombosis/orina , Trombosis de la Vena/patología

RESUMEN

BACKGROUND: Among cytokines- interleukins: -6 and -8 (IL-6, IL-8) and E-selectin (E-sel.), L-selectin (L-sel.) and intercellular cell adhesion molecule-1 (ICAM-1) are the most important links in the initiation of the inflammatory process. Taking into account that the inflammatory process is the basic stage of effective radioiodine therapy, we tried to compare the behaviour of the initial inflammatory factors in the early period of I-131 therapy (RAI) of hyperthyroidism. The aim of the study was to estimate the behaviour of IL-6, ICAM-1, E-selectin and L-selectin concentrations in the serum of patients with hyperthyroidism before and during I-131 therapy. MATERIAL AND METHODS: The groups of 26 patients with Graves' disease (GD) and 18 patients with toxic nodular goiter (TNG), aged 34-77, were studied. Control group (C) consisted of 10 healthy volunteers. For estimation of thyroid function serum concentrations of TSH, free T4 and free T3 were measured by IRMA or RIA kits (Polatom, Poland). IL-6, ICAM-1, E-selectin and L-selectin serum concentrations were determined using ELISA method by Bender kits (USA). Blood samples for all estimations were taken 10-12 days before and in 6th week after I-131 administration. Treatment dose of radioiodine was calculated, basing on modified equation for absorbed dose. RESULTS: Compared to control, no statistical differences in the levels of E-selectin (C--44.4 +/- 11 ng/ml) and L-selectin (C--842 +/- 168.9 ng/ml) were observed before treatment in the patients with GD (E-sel.--59.8 +/- 19.6 ng/ml; L-sel.--1288.2 +/- 273.5 ng/ml) and with TNG (E-sel.--61.5 +/- 18.4 ng/ml, L-sel.--1247.0 +/- 273.5 ng/ml) as well as in the 6th week after I-131 administration; values in GD group were: E-sel.--57.3 +/- 19.5 ng/ml, L-sel.--1142.4 +/- 193.4 ng/ml; in TNG group: E-sel.--62.1 +/- 20.6 ng/ml, L-sel.--1113.5 +/- 236.3 ng/ml. In comparison to control there was no difference in initial IL-6 levels either in GD or in TNG group, but a statistically important decrease was observed in the 6th week after I-131 administration in GD patients (C--2.07 +/- 0.2 ng/ml v. 1.79 +/- 0.16 ng/ml). ICAM-1 serum concentrations before treatment were elevated compared to control group (C--190.2 +/- 34.7 ng/ml) in both groups (GD--263.6 +/- 24.6 ng/ml, p < 0.05; TNG--251.4 +/- 36.1 ng/ml, p < 0.05). In GD patients a statistically significant increase of ICAM-1 was observed in the 6th week (301.1 +/- 33.2 ng/ml, p < 0.05) of RAI whereas in TNG group there was no statistical difference compared to initial values (249.7 +/- 42.6 ng/ml, N.S.). CONCLUSION: We conclude that ICAM-1 and IL-6 may be important factors in the estimation of the inflammatory processes in the thyroid gland during radioiodine therapy, especially GD disease. E- and L-selectins seem to be not helpful in the monitoring of the thyroid inflammatory changes during the early period of I-131 therapy.