Effects of arachidonic acid hydroperoxides on vascular and non-vascular smooth muscle.
The omega-6 and omega-9 hydroperoxides of arachidonic acid (AA) caused dose-dependent contraction of rabbit aortic strip (RAS) and guinea pig ileum (GPI) at concentrations between 5 and 200 microM. At these concentrations, arachidonic acid had no effect in these preparations. The contractions could not be blocked by indomethacin, methysergide, phenoxybenzamine, propranolol, diphenhydramine, scopolamine, or the SRS-A antagonist FPL-55712, but were abolished by the calcium channel blocker nimodipine. In both tissues, the hydroperoxides initiated a sustained contraction. The onset of GPI contraction however, was much faster than the response of RAS to these hydroperoxides. 15-HPETE produced a more sustained contraction than 12-HPETE in both RAS and GPI. These results suggest that hydroperoxides generated from AA by the action of lipoxygenase can directly induce smooth muscle contraction and this effect is probably mediated through altering calcium fluxes in these smooth muscle preparations.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001095:Arachidonic Acids / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D015289:Leukotrienes; D008054:Lipid Peroxides; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009539:Nicotinic Acids / Q000494:pharmacology; D009553:Nimodipine; D010545:Peroxides / Q000494:pharmacology*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001095:Arachidonic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D009539:Nicotinic Acids; D010545:Peroxides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009553:Nimodipine; C021201:12-HPETE; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid