Endothelium-Derived Hyperpolarizing Factor as a Reserve Defense Mechanism of the Vascular Control under Ionizing Radiation Impact

Membrane mechanisms underlying γ-radiation-induced changes in the contractile activity of the blood vessels were studied. The results obtained indicate that an exposure to γ-radiation inhibits the endothelium-dependent relaxation of isolated segments of the rat thoracic aorta due to a significant decrease in NO-component, while the component dependent on endothelial hyperpolarizing factor (EDHF) remains practically unchanged. This fact is confirmed by determining nitrites, NO metabolites: concentration of acetylcholine-stimulated nitrite anion derived by the aorta of exposed to γ-rays rats was significantly lower compared to the controls. Experiments on isolated rat aortic smooth muscle cells using whole-cell patch clamp technique demonstrated that irradiation resulted in a significant decrease in total outward potassium currents. However, an exposure to γ-radiation was without effect on K+-current through apamine-sensitive potassium channels, whereas the current through charybdotoxin-sensitive channels was significantly increased. The data suggest that EDHF is resistant to ionized radiation and may constitute a crucial reserve mechanism to maintain the blood flow under radiation. Therefore, it is likely that the subsequent studies related to EDHF identification will be important for new drug development and targeted pharmacological intervention at endothelium dysfunction in case of radiation impact.