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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

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Pharmacology & Pharmacy 2016年第1期7卷 81-88页

作者： Nikoloz V. Gongadze Tamara D. Kezeli Galina V. Sukoyan Zaza Chapichadze Nino M. Dolidze makrine mirziashvili Mariam Chipashvili Department of Medical Pharmacology and Pharmacotherapy Tbilisi State Medical University Tbilisi Georgia Department of Pharmacology Faculty of Medicine I. Javakhishvili Tbilisi State University Tbilisi Georgia International Scientific Centre of Introduction of New Biomedical Technology Tbilisi Georgia Department of Pharmacology State Regulation Agency for Medical Activities Ministry of Health and Social Affairs of Georgia Tbilisi Georgia

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®, 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® 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® 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® 91.6%, MB 55.8%). NADCIN® in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p ® of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.

关键词： Experimental Model of Nitroglycerin Tolerance Baroreflex Sensitivity Aldehyde Dehydrogenase Redox-Potential Splanchnic Sympathetic Nerve Activity

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