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Lazuko S.S., Medvedev М.N., Belyaeva L.E.
Inducible NO-synthase hyperexpression as an important cause of rats’ aortic ring endothelium-dependent dilatation enhancement and adrenoreactivity reduction in experimental diabetes mellitus
Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus

Vestnik VGMU. 2019;18(2):44-52.

Objectives. To determine the contribution of the inducible NO-synthase to mechanisms of isolated rats’ aortic rings endothelium-dependent vasodilatation and adrenoreactivity disorders in experimental diabetes mellitus.
Material and methods. Experiments were performed on rings of the aorta isolated from the bodies of female rats with experimental diabetes mellitus, that was modelled by means of the single intraperitoneal injection of streptozocin (50 mg/kg) dissolved in the citrate buffer (pH 4.5). Aortic rings specimens contracted in the isometric regimen were perfused with Krebs-Henseleit solution, aerated with carbogen (95% of O2 and 5% of CO2). Adrenoreactivity of aortic rings was assessed by their response to α1-adrenomimetic phenylephrine, that was added to the perfusion solution in increasing concentrations (from 10-15 up to 10-6М). To investigate endothelium-dependent aortic vasodilatation acetylcholine was infused in the perfusion bath at the doses from 1×10-10 up to 3×10-5М. To establish the role of iNOS in the mechanisms of aortic tone regulation high-selective enzyme blocker S-methylisothiourea (S-MT) was administered (10 mcМ, Sigma, USA). Immunohistochemical study of histological sections of aorta rings specimens was carried out with polyclonal antibodies (Abcam, UK) to iNOS (1:75) and eNOS (1:150). The obtained results were interpreted with the help of semiquantitative method assessing the intensity of slide mounts staining.
Results. It was shown that experimental diabetes mellitus produces pronounced endothelium-dependent aortic ring vasodilatation and diminished vasoconstriction due to nitric oxide hyperproduction mainly by iNOS. Moreover, decreased level of the eNOS expression and iNOS hyperexpression in endothelial cells of the aorta were detected.
Conclusions. Nitric monoxide, produced by iNOS, plays a key role in the adrenoreactivity reduction and enhancement of acetylcholine-induced vasodilatation of aortic rings isolated from rats after experimental diabetes mellitus.
Key words: inducible NO-synthase, diabetes mellitus, endothelium-dependent vasodilatation, adrenoreactivity.


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Information about authors:
Lazuko S.S. – Candidate of Biological Sciences, associate professor, head of the Chair of Normal Physiology, Vitebsk State Order of Peoples’ Friendship Medical University;
Medvedev M.N. – Candidate of Medical Sciences, associate professor of the Chair of Pathologic Anatomy with the course of Forensic Medicine, Vitebsk State Order of Peoples’ Friendship Medical University;
Belyaeva L.E. – Candidate of Medical Sciences, associate professor, head of the Chair of Pathologic Physiology, Vitebsk State Order of Peoples’ Friendship Medical University.

Correspondence address: Republic of Belarus, 210009, Vitebsk, 27 Frunze ave., Vitebsk State Order of Peoples’ Friendship Medical University, Chair of Normal Physiology. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Svetlana S. Lazuko.

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