Palytoxin-induced endothelium-dependent relaxation in the isolated rat aorta.

The effects of a potent marine toxin, palytoxin (PTX), were investigated on the contractile responses in the isolated rat aorta with or without endothelium. PTX in the concentrations of 10(-13)-10(-11) mol/l showed little effect on the resting tension of the vessel with or without endothelium. PTX, 10(-10) mol/l, induced a small contraction in the aorta without endothelium but not in the aorta with endothelium. When added during the sustained contraction induced by 10(-7) mol/l norepinephrine, 10(-12) mol/l PTX sometimes (6 out of 43 strips) augmented the norepinephrine-induced contraction whereas 10(-11)-10(-10) mol/l PTX induced a biphasic response which was composed of a transient augmentation followed by a relaxation. These effects of PTX were not observed in the aorta without endothelium. Influences of atropine (10(-6) mol/l), indomethacin (2.5 X 10(-5) mol/l), methylene blue (5 X 10(-6) mol/l), hydroquinone (10(-4) mol/l), phenidone (5 X 10(-5) mol/l), hemoglobin (10(-6) mol/l) and p-bromophenacyl bromide (5 X 10(-5) mol/l) on the PTX (10(-10) mol/l) induced responses were examined. Methylene blue, hydroquinone, phenidone, hemoglobin and p-bromophenacyl bromide inhibited both the PTX-induced augmentation and relaxation of the norepinephrine-induced contraction. The endothelium-dependent relaxation due to 3 X 10(-7) mol/l carbachol was inhibited by atropine, methylene blue, hydroquinone, phenidone, hemoglobin and p-bromophenacyl bromide. These results suggest that PTX acts on the endothelium, modifies the synthesis or release of endothelium-derived relaxing factor and thus changes the contractile response to norepinephrine in rat aorta.