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Article

Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model

1
Department of Biopharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland
2
Department of Pharmacology, Medical University of Bialystok, 15-222 Bialystok, Poland
3
University of Medical Science of Bialystok, 15-875 Bialystok, Poland
4
Department of Experimental and Clinical Pharmacology, University of Rzeszow, 35-959 Rzeszow, Poland
5
Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
6
National Drug and Alcohol Research Center, University of New South Wales, Sydney 2052, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Academic Editor: András Balla
Cells 2021, 10(2), 471; https://doi.org/10.3390/cells10020471
Received: 4 February 2021 / Revised: 18 February 2021 / Accepted: 19 February 2021 / Published: 22 February 2021
(This article belongs to the Special Issue Renin–Angiotensin–Aldosterone System)
We investigated the role of aldosterone (ALDO) in the development of arterial thrombosis in streptozotocin-induced diabetic rats. To evaluate the effect of endogenous ALDO, the rats underwent adrenalectomy (ADX). ADX reduced the development of arterial thrombosis. A 1 h infusion of ALDO (30 μg/kg/h) enhanced thrombosis in adrenalectomized rats, while this effect was potentiated in diabetic rats. ALDO shortened bleeding time, increased plasma levels of tissue factor (TF) and plasminogen activator inhibitor, decreased plasma level of nitric oxide (NO) metabolites, and increased oxidative stress. Moreover, 2 h incubation of human umbilical vein endothelial cells (HUVECs) with ALDO (10−7 M) disrupted hemostatic balance in endothelial cells in normoglycemia (glucose 5.5 mM), and this effect was more pronounced in hyperglycemia (glucose 30 mM). We demonstrated that the acute ALDO infusion enhances arterial thrombosis in rats and hyperglycemia potentiates this prothrombotic effect. The mechanism of ALDO action was partially mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors and related to impact of the hormone on primary hemostasis, TF-dependent coagulation cascade, fibrinolysis, NO bioavailability, and oxidative stress balance. Our in vitro study confirmed that ALDO induces prothrombotic phenotype in the endothelium, particularly under hyperglycemic conditions. View Full-Text
Keywords: aldosterone; adrenalectomy; diabetes; thrombosis; mineralocorticoid receptor; glucocorticoid receptor aldosterone; adrenalectomy; diabetes; thrombosis; mineralocorticoid receptor; glucocorticoid receptor
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MDPI and ACS Style

Gromotowicz-Poplawska, A.; Szoka, P.; Zakrzeska, A.; Kolodziejczyk, P.; Marcinczyk, N.; Szemraj, J.; Tutka, P.; Chabielska, E. Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model. Cells 2021, 10, 471. https://doi.org/10.3390/cells10020471

AMA Style

Gromotowicz-Poplawska A, Szoka P, Zakrzeska A, Kolodziejczyk P, Marcinczyk N, Szemraj J, Tutka P, Chabielska E. Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model. Cells. 2021; 10(2):471. https://doi.org/10.3390/cells10020471

Chicago/Turabian Style

Gromotowicz-Poplawska, Anna, Piotr Szoka, Agnieszka Zakrzeska, Patrycjusz Kolodziejczyk, Natalia Marcinczyk, Janusz Szemraj, Piotr Tutka, and Ewa Chabielska. 2021. "Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model" Cells 10, no. 2: 471. https://doi.org/10.3390/cells10020471

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