Влияние донатора no на параметры гемодинамики и функцию эндотелия при длительной блокаде СВ1 рецепторов каннабиноидов в эксперименте

Abstract

In the paper, topical issues of studying the mechanisms of adaptation of the cardiovascular system to the effects of blockade of cannabinoid receptors against the background of the introduction of a nitric oxide donor. The purpose of this study was to evaluate the changes in ultrasonic characteristics of hemodynamics and the function of the endothelium of the abdominal aorta on the model of accompanying the prolonged blockade of CB1 receptors of cannabinoids by the donor of nitric oxide tivortin aspartate in experimental animals. The studies were performed on three comparable groups of hundred-day 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 rats, daily injected with rimonabant hydrochloride solution at a rate of 10 mg-kg-1; The third is the animals who received a solution of rimonabant hydrochloride at a rate of 10 mg-kg-1 and a solution of tivortin aspartate at a dose of 100 mg of L-arginine aspartate per kg of animal weight per day per os daily. During ultrasound in the B-mode, the intraluminal diameter of the vessel, the thickness of the intima-media complex, endothelium-dependent and endothelium-independent dilation were quantified. In the regime of pulsed wave Dopplerography, the quantitative characteristics of the blood flow were investigated: peak systolic blood flow velocity, maximum terminal diastolic blood flow velocity, resistance index and systolodiastolic ratio. The average blood flow velocity was calculated by the formula.Changes in the diameter of the vessel were estimated as a percentage of the initial value. Endothelium-dependent and endothelium-independent dilation was assessed as a change in the diameter of the abdominal aorta after bolus administration of the dilatation mediators to the femoral vein, respectively: acetylcholine chloride (at the rate of 40 mgwkg-1 animal weight) and nitroglycerin (based on 2 mgwkg-1mass of the animal). Based on the results of the variational analysis of hemodynamic parameters, some features of the restructuring of the vascular wall response are revealed depending on the blockade of the cannabinoid receptors and the maintenance of L-arginine with aspartate. In particular, prolonged blockade of CB1 receptors of cannabinoids in the animals under study leads to the development of endothelial dysfunction, a decrease in the intraluminal diameter of the abdominal aorta and a decrease in the average blood flow velocity while maintaining the elastically elastic properties of the vascular wall. This affects the sensitivity of the vessel wall to nitrogen oxide, which is manifested by its insufficient dilatation after the administration of nitroglycerin. When accompanied by a prolonged blockade of CB1 receptors in cannabinoids by the administration of L-arginine aspartate, the intraluminal diameter, structure and function of the endothelium of the abdominal aorta persist, and the sensitivity of the vessel wall to nitroglycerin increases. However, a hemodynamic disorder is formed and the stiffness of the vascular wall is increased. To understand the mechanisms of development of endothelial dysfunction with the combination of donators of nitric oxide with the blockade of CB1 receptors of cannabinoids, additional studies are needed.