%0 Journal Article
%T Deterioration in Hemodynamics Reaction, Baroreflex Sensitivity, Sympathetic Nerve Activity and Redox State of Thoracic Aorta in the Experimental Model of Nitrate Tolerance and Its Pharmacological Correction
%A Nikoloz V. Gongadze
%A Tamara D. Kezeli
%A Galina V. Sukoyan
%A Zaza Chapichadze
%A Nino M. Dolidze
%A Makrine Mirziashvili
%A Mariam Chipashvili
%J Pharmacology & Pharmacy
%P 81-88
%@ 2157-9431
%D 2016
%I Scientific Research Publishing
%R 10.4236/pp.2016.71011
%X Continuous treatment with organic nitrates causes nitrate tolerance and provides evidence for a relationship between mitochondrial complex 1 activity and mitochondrial aldehyde dehydrogenase-2 (ALDH-2) with disturbances of the hemodynamics reaction during nitroglycerin (NTG) tolerance (NTGT). The purpose of this study was the evaluation of efficacy of original oxidized form NAD-containing drug, NADCIN<sup>&reg</sup>, on hemodynamic reactions, baroreflex sensitivity (BRS) and reflex control of splanchnic sympathetic nerve activity (SSNA), level of redox-potential, activity of ALDH-2 and superoxide anion generation in aortic tissue in rat model of NTGT. Five groups (7 - 9 each) of male Wistar rats, including control, acute i.v. NTG (150 mcg/kg) administration, NTG tolerance NTGT treatment with NADCIN<sup>&reg</sup> 8 mg/kg and methylene blue (MB, 2.5 mg/kg) were used. NTGT in rats was accompanied with the greatly attenuation of hemodynamics reaction, BRS, the decreasing of the ability to reflex control of SSNA without pronounce overexpression of endothelin-1 in vessels (aorta). In NTGT rats i.v. NTG along induced less hypotensive reactions and alterations in heart period vs single NTG treated group, more expressively decreased BRS (-34%) and reflex control of SSNA (-18%). NADCIN<sup>&reg</sup> significantly inhibits tolerance-inducing properties of the prolonged nitroglycerin infusion (max decrease of blood pressure response to nitroglycerin injection, % of normal controls: NTGT 51.2%, NADCIN<sup>&reg</sup> 91.6%, MB 55.8%). NADCIN<sup>&reg</sup> in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p &lt; 0,05), reflex control of SSNA (+29.4%, p &lt; 0.05) and reversed the decreasing of NAD/NADH ratio, ALDH-2 activity and decreasing in superoxide generation in thoracic aortic tissue. Thus, course treatment with NADCIN<sup>&reg</sup> of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.
%K Experimental Model of Nitroglycerin Tolerance
%K Baroreflex Sensitivity
%K Aldehyde Dehydrogenase
%K Redox-Potential
%K Splanchnic Sympathetic Nerve Activity
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=63135