Systemic Administrations of Water-Dispersible Single-Walled Carbon Nanotubes: Activation of NOS in Spontaneously Hyperte

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Neurophysiology, Vol. 52, No. 2, March, 2020

Systemic Administrations of Water-Dispersible Single-Walled Carbon Nanotubes: Activation of NOS in Spontaneously Hypertensive Rats L. M. Shapoval,1 O. V. Dmytrenko,1 V. F. Sagach,1 S. V. Prylutska,2 S. V. Khrapatiy,2 D. O. Zavodovskyi,1 Yu. I. Prylutskyy,2 N. Tsierkezos,3 and U. Ritter3 Received August 12, 2019 Priority data have been obtained on the effects of repeated systemic administrations of water-dispersible single-walled carbon nanotubes (SWCNTs) to spontaneously hypertensive rats with respect to constitutive NO-synthase (cNOS). As is known, NO is an inhibitory transmitter in the cardiovascular system. It was found that the systemic (i.p., subcutaneous, and i.m.) introductions of SWCNTs during two weeks resulted in considerable elevations of the NO2– level (a marker of NO bioavailability) in the blood of experimental hypertensive animals. Thus, SWCNTs may be used in the future for antihypertensive therapy as a novel agent capable of activating cNOS and, thus, increasing the NO production in central and peripheral elements of the cardiovascular system.

Keywords: single-walled carbon nanotubes, constitutive nitric oxide synthase (cNOS), spontaneously hypertensive rats, biochemical methods.

INTRODUCTION Carbon nanotubes (single- and multi-walled CNTs) are nanomaterials attracting significant attention due to their great potential for biomedical implementations [1, 2]. It has been reported that single-walled CNTs (SWCNTs) can affect neuronal activity [3], most likely at the level of ion channels [4]. SWCNTs were found to possess a noticeable neuroprotective capability in both in vivo and in vitro experiments [5]. There is evidence that substances delivered by functionalized CNTs are capable of reducing neurodegeneration and promoting recovery from brain ischemic insult [6]. Scaffolds for cardiac tissue engineering based on CNTs seem to be a powerful tool to improve the cardiac activity, since they have been recently found to support growth of cardiac cells and to improve proliferation, maturation, and electrical behavior of cardiomyocytes [7]. Application of

Bogomolets Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine Taras Shevchenko National University of Kyiv, Kyiv, Ukraine 3 Ilmenau University of Technology, Institute of Chemistry and Biotechnology, Ilmenau, Germany Correspondence should be addressed to Yu. I. Prylutskyy (e-mail: [email protected]). 1 2

SWCNTs induced vasodilation in isolated rat aortic preparations [8]. It has been suggested that intratracheally administered SWCNTs affect autonomic cardiovascular regulation through the baroreflex mechanisms [9]. Stereotactic injections of SWCNTs in the medullary cardiovascular nuclei of spontaneously hypertensive rats (SHRs) result in lowering of the blood pressure [10]. It has been reported that SWCNTs can penetrate the cells via either an endocytosis-dependent pathway or via diffusion [11, 12]. The process of SWCNTs internalization depends on several parameters, such as their size, length, functional g