The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats

Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods. Eighty female SD rats were divided into...

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Main Authors: Dragan Manojlović, Ana Stupin, Anita Matić, Zrinka Mihaljević, Sanja Novak, Ines Drenjančević
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2019/5410108
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author Dragan Manojlović
Ana Stupin
Anita Matić
Zrinka Mihaljević
Sanja Novak
Ines Drenjančević
author_facet Dragan Manojlović
Ana Stupin
Anita Matić
Zrinka Mihaljević
Sanja Novak
Ines Drenjančević
author_sort Dragan Manojlović
collection DOAJ
description Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods. Eighty female SD rats were divided into four groups: nonovariectomized healthy (non-OVX-CTR) and diabetic (non-OVX-DM) rats and ovariectomized healthy (OVX-CTR) and diabetic (OVX-DM) rats. Bilateral ovariectomy was performed at the age of 5 weeks, and type 1 DM was induced by streptozotocin at the age of 6 weeks. At the age of 12 weeks, acetylcholine-induced relaxation (AChIR) was assessed in aortic rings in the absence/presence of L-NAME, Indomethacin, and MS-PPOH. Aortic tissue mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane synthase 1 (TBXAS1), CYP4A1, CYP4A3, and CYP2J3, as well as plasma oxidative stress, was measured. Results. AChIR did not differ in non-OVX-DM rats compared to non-OVX-CTR ones. AChIR was significantly reduced in the OVX-DM group compared to the OVX-CTR group. MS-PPOH did not reduce AChIR in OVX-DM rats as it did in OVX-CTR ones. CYP4a3 mRNA expression in OVX-DM rats was significantly lower compared to that in the OVX-CTR group. Conclusions. Female sex hormones may protect vasorelaxation in type 1 diabetic rats. Type 1 diabetes impairs vasorelaxation in response to ACh in ovariectomized rats (but not in nonovariectomized rats) by affecting vasorelaxation pathways mediated by EETs.
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spelling doaj-art-76b49e2ec0044ffa992a47947be3c2182025-02-03T05:50:59ZengWileyInternational Journal of Endocrinology1687-83371687-83452019-01-01201910.1155/2019/54101085410108The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley RatsDragan Manojlović0Ana Stupin1Anita Matić2Zrinka Mihaljević3Sanja Novak4Ines Drenjančević5Department of Surgery, General Hospital Vukovar, Vukovar, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, CroatiaAim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods. Eighty female SD rats were divided into four groups: nonovariectomized healthy (non-OVX-CTR) and diabetic (non-OVX-DM) rats and ovariectomized healthy (OVX-CTR) and diabetic (OVX-DM) rats. Bilateral ovariectomy was performed at the age of 5 weeks, and type 1 DM was induced by streptozotocin at the age of 6 weeks. At the age of 12 weeks, acetylcholine-induced relaxation (AChIR) was assessed in aortic rings in the absence/presence of L-NAME, Indomethacin, and MS-PPOH. Aortic tissue mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane synthase 1 (TBXAS1), CYP4A1, CYP4A3, and CYP2J3, as well as plasma oxidative stress, was measured. Results. AChIR did not differ in non-OVX-DM rats compared to non-OVX-CTR ones. AChIR was significantly reduced in the OVX-DM group compared to the OVX-CTR group. MS-PPOH did not reduce AChIR in OVX-DM rats as it did in OVX-CTR ones. CYP4a3 mRNA expression in OVX-DM rats was significantly lower compared to that in the OVX-CTR group. Conclusions. Female sex hormones may protect vasorelaxation in type 1 diabetic rats. Type 1 diabetes impairs vasorelaxation in response to ACh in ovariectomized rats (but not in nonovariectomized rats) by affecting vasorelaxation pathways mediated by EETs.http://dx.doi.org/10.1155/2019/5410108
spellingShingle Dragan Manojlović
Ana Stupin
Anita Matić
Zrinka Mihaljević
Sanja Novak
Ines Drenjančević
The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats
International Journal of Endocrinology
title The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats
title_full The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats
title_fullStr The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats
title_full_unstemmed The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats
title_short The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats
title_sort role of epoxyeicosatrienoic acids in diabetes mellitus induced impaired vascular relaxation of aortic rings in ovariectomized sprague dawley rats
url http://dx.doi.org/10.1155/2019/5410108
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