Effect of cannabinoids CB1 receptors blockade on hemodynamic parameters and endothelial function at the immobilization stress in the experiment
DOI:
https://doi.org/10.14739/2310-1210.2017.6.114704Keywords:
cannabinoid receptors, endothelial dysfunction, abdominal aorta, hemodynamicsAbstract
The aim of the study was to evaluate the response of hemodynamic parameters and changes in endothelial function in modeling of CB1 cannabinoid receptors blockade in chronic stress.
Materials and мethods. The study was performed on four groups of hundred-day-old rats, which were examined by ultrasonic scanning during the ten-day period of the experiment. The first group consisted of intact animals; the second group – animals, which were exposed to immobilization stress; the third – animals which were given a solution of rimonabant hydrochloride at the rate of 10 mg×kg-1 of animal weight per day daily per os; the fourth group consisted of animals which daily received a solution of rimonabant hydrochloride at the rate of 10 mg×kg-1 of animal weight per day and were exposed to immobilization stress.
The intraluminal vessel diameter, the intima-media complex thickness, endothelium-dependent and endothelium-independent dilation were quantified in the ultrasound examination. Quantitative characteristics of the blood flow were studied: peak systolic velocity, end diastolic velocity, resistive index and peak-systolic/end-diastolic ratio, and estimated mean blood flow velocity.
Results. It has been found that the effect of chronic immobilization stress in 100-day-old male rats causes intima-media complex structure and thickness change, endothelial dysfunction and increase in the abdominal aorta intraluminal diameter. Hemodynamics changes are characterized by a decrease in the average blood flow velocity and an increase in the values of indices characterizing the vascular wall peripheral resistance.
Prolonged blockade of cannabinoids CB1 receptors leads to endothelial dysfunction development, a decrease in the intraluminal diameter of the abdominal aorta and a decrease in the average blood flow velocity while vascular wall elastic properties maintaining. This affects the sensitivity of cardiovascular system to nitrogen oxide, which is manifested by test vessel insufficient dilatation after nitroglycerin administration.
The endothelium function, the structure and elasticity of vessel wall in case of chronic immobilization stress and cannabinoid CB1 receptors blockade combination are maintained. However, a significant decrease in the speed characteristics of hemodynamics develops.
Conclusions. The results of the studies indicate that in case of chronic immobilization stress in hundred-day-old rats remodeling of the vessel wall by an eccentric type and endothelial dysfunction develop. The change in the velocity characteristics of hemodynamics is characterized by a decrease in the average blood flow velocity and an increase in the abdominal aorta wall stiffness.
Long cannabinoids CB1 receptors blockade in the comparable group of rats causes remodeling of vessel wall in concentric manner with both endothelium-dependent and endothelium-independent dilation disturbance. Changes in the speed characteristics of hemodynamics are characterized by a decrease in the average blood flow velocity while vascular wall elastic properties maintaining.
Rimonabant hydrochloride administration in healthy one-hundred-day rats with chronic immobilization stress maintains the vessel wall structure and endothelial function. However, a significant decrease in the speed characteristics of hemodynamics develops while vascular wall elastic properties maintaining.
References
Kotsis, V., Stabouli, S., Karafillis, I., & Nilsson, P. (2011) Early vascular aging and the role of central blood pressure. J Hypertens, 29(10), 1847–1853. doi: 10.1097/HJH.0b013e32834a4d9f.
Morena, M., Patel, S., Bains, J. S., & Hill, M. N. (2016) Neurobiological interactions between stress and the endocannabinoid system. Neuropsychopharmacology, 41(1), 80–102. doi: 10.1038/npp.2015.166.
Malinowska, B., Baranowska-Kuczko, M., & Schlicker, E. (2012) Triphasic blood pressure responses to cannabinoids: do we understand the mechanism? Br. J. Pharmacol, 165, 2073–2088. doi: 10.1111/j.1476-5381.2011.01747.x.
Pacher, P., Bátkai, S., & Kunos, G. (2005) Cardiovascular pharmacology of cannabinoids. Handb. Exp. Pharmacol., 168, 599–625. doi: 10.1007/3-540-26573-2_20.
Granjeiro, E. M., Gomes, F. V., Guimaraes, F. S., Correa, F. M., & Resstel, L. B. (2011) Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress. Pharmacol Biochem Behav, 99(4), 743–748. doi: 10.1016/j.pbb.2011.06.027.
Tiyerili, V., Zimmer, S., Jung, S., Wassmann, K., Naehle, C. P., Lutjohann, D., et al. (2010) CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function. Basic Res Cardiol, 105(4), 465–477. doi: 10.1007/s00395-010-0090-7.
Szekeres, M., Nadasy, G. L., Turu, G., Soltesz-Katona, E., Toth, Z. E., Balla, A., et al. (2011) Angiotensin II induces vascular endocannabinoid release, which attenuates its vasoconstrictor effect via CB1 cannabinoid receptors. J Biol Chem, 287(37), 31540–31550. doi: 10.1074/jbc.M112.346296.
Buwembo, A., Long, H., & Walker, C. D. (2013) Participation of endocannabinoids in rapid suppression of stress responses by glucocorticoids in neonates. Neuroscience, 249, 154–161. doi: 10.1016/j.neuroscience.2012.10.057.
Reece, A. S., Norman, A., & Hulse, G. K. (2016) Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study. BMJ Open., 6(11), e011891. doi: 10.1136/bmjopen-2016-011891.
Slavic, S., Lauer, D., Sommerfeld, M., Kemnitz, U. R., Grzesiak, A., Trappiel, M., et al. (2013) Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome. Journal of Molecular Medicine, 91(7), 811–823. doi: 10.1007/s00109-013-1034-0.
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