DOI: https://doi.org/10.22263/2312-4156.2016.2.27
Zagayko A.L., Briukhanova T.A.
The study of the influence of affinely purified antibodies against endocannabinoid receptor on endothelium functional status in experimental insulin resistance
National University of Pharmacy, Kharkov, Ukraine
Vestnik VGMU. 2016;15(2):27-33.
Abstract.
Objectives. Metabolic syndrome (MS) is associated with the high risk of cardiovascular complications development on its background. Cardiovascular continuum formation is due to endothelial dysfunction (ED) occurrence that is characterized by the imbalance of vasoconstrictor and vasodilator factors production, with the prevalence of the latter ones. According to several authors’ data, activation of endocannabinoid system (ECS) plays an important role in the ED pathogenesis. Therefore, the aim of our work was to study the effect of the drug based on affinely purified antibodies against type 1 endocannabinoid receptor, on certain parameters of endothelium functional status in the rats with experimental insulin resistance (IR).
Material and methods. Wistar male rats which had been kept on the diet enriched by fructose were used in the experiment. Intraperitoneal administration of low dexamethasone doses during 5 weeks on the background of the diet with high fructose content resulted in the IR development. The studied drug was administered intragastrically during 3 weeks. The content of S-nitrosothiols (S-NO), endothelin-1 (ET-1) and their ratio in the blood were determined. The investigations were carried out according to the current principles of bioethics.
Results. Long-term administration of dexamethasone low doses on the background of the diet with high fructose content led to the formation of IR syndrome. Animals with MS showed a statistically reliable increase of ET-1 content (2,62 times) with the simultaneous reduction of S-NO content (4,08 times) with regard to the indices of healthy animals. The calculation of the relationship coefficient of ET-1/S-NO testified to the development of endothelial dysfunction on the IR background. A similar though less pronounced dynamics of the examined parameters against the background of the studied drug application was observed that was probably due to the mechanism of the drug action.
Conclusions. The dynamics of ED indicators in experimental IR signifies that the search for the new methods to correct the designated changes for the prevention of cardiovascular complications development against MS is promising.
Key words: endocannabinoids, endothelial dysfunction, metabolic syndrome, insulin resistance.
References
1. Carbone F, Mach F, Vuilleumier N, Montecucco F. Cannabinoid receptor type 2 activation in atherosclerosis and acute cardiovascular diseases. Curr Med Chem. 2014;21(35):4046-58.
2. Farooqui AA, Farooqui T, Panza F, Frisardi V. Metabolic syndrome as a risk factor for neurological disorders. Cell Mol Life Sci. 2012 Mar;69(5):741-62.
3. Gallagher EJ, Leroith D, Karnieli E. The metabolic syndrome-from insulin resistance to obesity and diabetes. Med Clin North Am. 2011 Sep;95(5):855-73.
4. Holman EA, Guijarro A, Lim J, Piomelli D. Effects of acute stress on cardiac endocannabinoids, lipogenesis, and inflammation in rats. Psychosom Med. 2014 Jan;76(1):20-8.
5. Horváth B, Mukhopadhyay P, Haskó G, Pacher P. The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. Am J Pathol. 2012 Feb;180(2):432-42.
6. Kheyfets IA, Bugaeva LI, Vorob'eva TM, Dugina JL, Lebedeva SA, Petrov VI et al. Experimental study of the effects of Dietressa, a new weight-reducing drug. Bull Exp Biol Med. 2012 Jan;152(3):321-4.
7. Knowles MD, de la Tremblaye PB, Azogu I, Plamondon H. Endocannabinoid CB1 receptor activation upon global ischemia adversely impact recovery of reward and stress signaling molecules, neuronal survival and behavioral impulsivity. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Apr;66:8-21.
8. Lobato NS, Filgueira FP, Akamine EH, Tostes RC, Carvalho MH, Fortes ZB. Mechanisms of endothelial dysfunction in obesity-associated hypertension. Braz J Med Biol Res. 2012 May;45(5):392-400.
9. Montecucco F, Di Marzo V. At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction. Trends Pharmacol Sci. 2012 Jun;33(6):331-40.
10. Ntaios G, Gatselis NK, Makaritsis K, Dalekos GN. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis. 2013 Apr;227(2):216-21.
11. Pacher P, Kunos G. Modulating the endocannabinoid system in human health and disease–successes and failures. FEBS J. 2013 May;280(9):1918-43.
12. Persidsky Y, Fan S, Dykstra H, Reichenbach NL, Rom S, Ramirez SH. Activation of Cannabinoid Type Two Receptors (CB2) Diminish Inflammatory Responses in Macrophages and Brain Endothelium. J Neuroimmune Pharmacol. 2015 Jun;10(2):302-8.
13. Rajesh M, Bátkai S, Kechrid M, Mukhopadhyay P, Lee WS, Horváth B et al. Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy. Diabetes. 2012 Mar;61(3):716-27.
14. Ramirez SH, Haskó J, Skuba A, Fan S, Dykstra H, McCormick R et al. Activation of cannabinoid receptor 2 attenuates leukocyte–endothelial cell interactions and blood–brain barrier dysfunction under inflammatory conditions. J Neurosci. 2012 Mar;32(12):4004-16.
15. Rom S, Persidsky Y. Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation. J Neuroimmune Pharmacol. 2013 Jun;8(3):608-20.
16. Romeo GR, Lee J, Shoelson SE. Metabolic syndrome, insulin resistance, and roles of inflammation–mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1771-6.
17. Stanley CP, Wheal AJ, Randall MD, O'Sullivan SE. Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes. Eur J Pharmacol. 2013 Nov;720(1-3):376-82.
18. Steffens S, Pacher P. The activated endocannabinoid system in atherosclerosis: driving force or protective mechanism? Curr Drug Targets. 2015;16(4):334-41.
19. Sugamura K, Sugiyama S, Nozaki T, Matsuzawa Y, Izumiya Y, Miyata K et al. Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation. 2009 Jan;119(1):28-36.
20. Zagayko AL, Bryukhanova TO, Shkapo AІ. Moduliuiuchii vpliv sibutramіnu na zmіni metabolіzmu, zumovlenі eksperimental'noiu іnsulіnorezistentnіstiu v shchurіv [The modulating influence of a sibutramin on the changes of a metabolism caused by an experimental insulinorezistentnost at rats]. Farmakologіia ta lіkars'ka toksikologіia. 2015;(3):62-9.
21. Zagayko AL, Bryukhanova TO, Shkapo AІ. Modifіkatsіia metodu modeliuvannia eksperimental'noї іnsulіnorezistentnostі u shchurіv [Modification of a method of modeling of an experimental insulinorezistentnost at rats]: іnformatsіinii list. Kiev, Ukraine; 2015. N 86. 7 p.
