PP.41.11

Abstract

Objective: Hypoxia is a pathological process, emerging due to oxygen starvation of cells and leading to destructive changes in tissues. It is shown that hypoxia triggers of metabolic disorders, which can lead to damage of contractile ability of the vascular smooth muscle cells (VSMC). It is assumed that one of the possible mechanisms of action of hypoxia on the contractile function of smooth muscle cells (SMCs) is activated K+ channels of plasma membrane. Design and method: Contractile activity of endothelium-denuded SMCs from rat aorta in hypoxia was studied by the method of mechanography (Myobath II/Lab-Trax-4/16). Hypoxic conditions were created by bubbling nitrogen gas (95%N2/5%O2) through the solutions for 15 minutes immediately before the experiment. Contractions induced by membrane depolarization of VSMC in a high-potassium solution (30 mM KCl) or phenylephrine (PE, 1 μM). Solutions of tetraethylammonium (TEA,10 mM), 4-aminopyridine (4-AP, 1 mM) and glibenclamide (10 μM) were tested. Results: Under hypoxic conditions decreased the amplitude of the contractile response SMCs to high-potassium solution and PE (83.1 ± 2.9%, 73.4 ± 2.5% (n = 8, p < 0.05), respectively) from the control in normoxic conditions. Addition of TEA on the background of a high-potassium contraction in hypoxia resulted in increased mechanical tension of segments to 109.7 ± 2.1% (n = 8, p < 0.05), and phenylephrine to 125.3 ± 3.4% (n = 8, p < 0.05) from control during hypoxia. 4-AP in hypoxia increases the amplitude of the contractile response SMCs to high-potassium solution (110.9 ± 2.8% (n = 8, p < 0.05)) and PE-induced (111.3 ± 1.9% (n = 8, p < 0.05)) from control in hypoxia. Glibenclamide increases amplitude of PE-induced contraction of SMC to 107.8 ± 2.6% (n = 8, p < 0.05) and had no significant effect on high-potassium contractions of SMCs in hypoxia. Conclusions: Thus, hypoxia has an inhibitory effect on the contractile activity of VSMC. Hypoxia cause decreased amplitude of high-potassium solution and PE-induced contractions, in a greater extent in PE-induced contractions. This effect was associated with opening of voltage-dependent potassium channels, and by the action of phenylephrine - ATP-sensitive potassium channels of SMCs.