[Current concepts on the mechanisms of hypoxic effects on vascular tonus]

It is well known that hypoxia causes smooth muscle relaxation of the majority of mammalian systemic blood vessels, whereas smooth muscles in the pulmonary and large coronary arteries constrict under hypoxia. The review describes a modern concept of the mechanisms involved in the hypoxic vasoconstriction and vasodilatation. Cationic channels of a plasma membrane, the contractile apparatus, and mitochondria are the main oxygen sensors in the vascular smooth muscle cells. Hypoxic vasodilatation is mediated mainly by a decrease in the voltage-dependent Ca2+ entry, decrease in Ca2+ sensitivity of the contractile apparatus, and activation of ATP-dependent K+ channels. This process also involves endothelium derived nitric oxide. Hypoxic vasoconstriction mechanisms may be related to voltage-gating K+ channels inhibition, Ca2+ release from intracellular stores and inactivation of Ca2+ activated K+ channels each of them leads to increase in intracellular Ca2+ concentration. Platelet-activating factor, prostaglandins F2 alpha, E2, tromboxan B2, leucotriens C4 and D4 also contribute to hypoxic vasoconstriction. Glycolysis which intensity increases in hypoxia, and electron transport chain which generates the reactive oxygen species play the important role in the development of hypoxic pulmonary vasoconstriction. They possess the ability to change redox state in the cells and therefore to modulate the activity of the cationic channels. Hypoxia also leads to a proliferation of smooth muscles in the vascular wall. Better understanding of the underlying hypoxia-related mechanisms is vital for the explanation of enhanced blood flow under hypoxia, and is absolutely necessary for creating new effective antihypoxic drugs.