Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model
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)...
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MDPI AG
2021-02-01
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| author | Anna Gromotowicz-Poplawska Piotr Szoka Agnieszka Zakrzeska Patrycjusz Kolodziejczyk Natalia Marcinczyk Janusz Szemraj Piotr Tutka Ewa Chabielska |
| author_facet | Anna Gromotowicz-Poplawska Piotr Szoka Agnieszka Zakrzeska Patrycjusz Kolodziejczyk Natalia Marcinczyk Janusz Szemraj Piotr Tutka Ewa Chabielska |
| author_sort | Anna Gromotowicz-Poplawska |
| collection | DOAJ |
| description | 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<sup>−7</sup> 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. |
| first_indexed | 2024-03-09T00:37:23Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:37:23Z |
| publishDate | 2021-02-01 |
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| series | Cells |
| spelling | doaj.art-50109c19583140008a86d8f18879fb652023-12-11T18:01:55ZengMDPI AGCells2073-44092021-02-0110247110.3390/cells10020471Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis ModelAnna Gromotowicz-Poplawska0Piotr Szoka1Agnieszka Zakrzeska2Patrycjusz Kolodziejczyk3Natalia Marcinczyk4Janusz Szemraj5Piotr Tutka6Ewa Chabielska7Department of Biopharmacy, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Pharmacology, Medical University of Bialystok, 15-222 Bialystok, PolandUniversity of Medical Science of Bialystok, 15-875 Bialystok, PolandDepartment of Experimental and Clinical Pharmacology, University of Rzeszow, 35-959 Rzeszow, PolandDepartment of Biopharmacy, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Experimental and Clinical Pharmacology, University of Rzeszow, 35-959 Rzeszow, PolandDepartment of Biopharmacy, Medical University of Bialystok, 15-222 Bialystok, PolandWe 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<sup>−7</sup> 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.https://www.mdpi.com/2073-4409/10/2/471aldosteroneadrenalectomydiabetesthrombosismineralocorticoid receptorglucocorticoid receptor |
| spellingShingle | Anna Gromotowicz-Poplawska Piotr Szoka Agnieszka Zakrzeska Patrycjusz Kolodziejczyk Natalia Marcinczyk Janusz Szemraj Piotr Tutka Ewa Chabielska Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model Cells aldosterone adrenalectomy diabetes thrombosis mineralocorticoid receptor glucocorticoid receptor |
| title | Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model |
| title_full | Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model |
| title_fullStr | Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model |
| title_full_unstemmed | Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model |
| title_short | Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model |
| title_sort | hyperglycemia potentiates prothrombotic effect of aldosterone in a rat arterial thrombosis model |
| topic | aldosterone adrenalectomy diabetes thrombosis mineralocorticoid receptor glucocorticoid receptor |
| url | https://www.mdpi.com/2073-4409/10/2/471 |
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