INFLUENCE OF SYNTHETIC ANALOG OF PLATELET ACTIVATION FACTOR 1-ALKYL-2-ALKYLCARBOMOILGLICERINE ON VASCULAR SMOOTH MUSCLE CELLS CONTRACTILE PROPERTIES

Abstract

Objective. To study the effect of the synthetic analog of the platelet activation factor (based on the 1-alkyl-2-alkylcarbamoyl-glycerol) on the tone of vascular smooth muscle cells and hemodynamic parameters. Design and methods. We studied the vasodilator properties of 1-O-hexadecyl-2-O-methylcarbamoylglycerol, the substance from the group of 1-alkyl-2-alkylcarbamoylglycerols. Systemic arterial pressure, stroke volume and heart rate were recorded by the Biopac hardware complex in Wistar rats 3 hours after intragastric administration of the drug. We studied (the Myobath II Tissue bath system) mechanical tension of isolated aortic segments from Wistar and SHR rats precontracted with phenylephrine and nonisosomotic solutions. Using the Wire Myograph 620M system, we recorded changes in the contractility of the small mesenteric arteries, the artery of the gastrocnemius muscle and the renal interlobar arteries of the Wistar rats precontracted with methoxamine. Results. 1-O-hexadecyl-2-O-methylcarbamoylglycerol decreased arterial pressure in Wistar rats after intragastric administration due to the decrease in specific peripheral resistance, but does not exert an evident relaxation acting on isolated vessels pre-reduced by activation of α1-adrenoreceptors with phenylephrin and methoxamine. 1-O-hexadecyl-2-O-methylcarbamoylglycerol reduced the hyper-, hypo-, and isoosmotic contraction of the aortic segments from Wistar rats, but increased (isoosmotic contraction) or did not change (hyper- and hypoosmotic contraction) it in the vessels obtained from SHR rats. Conclusions. The pressure reducing effect of 1-O-hexadecyl-2-O-methylcarbamoylglycerol is not due to direct action on vascular cells. It might involve nervous/humoral mechanisms of blood pressure regulation. However, 1-O-hexadecyl-2-O-methylcarbamoylglycerol reduces the contraction amplitude induced by incubation in the non-isoosmotic environment in normotensive rats. However, the effect is not present in hypertensive rats indicating the possible involvement of NKCC in the mechanisms of the drug substance.