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Phenylephrine induces endothelium-independent rhythmic contractions in ryanodine-treated rabbit mesenteric arteries. To elucidate the ionic mechanism of this rhythmic behaviour, rabbit mesenteric arterial rings were suspended in an organ chamber for isometric tension studies. Yohimbine, propranolol, and atropine had no effect on these contractions, minimizing the possibility that transmitter release from nerve terminals was involved. Additionally, the oscillatory contractions were not altered by diphenhydramine, cimetidine, and indomethacin, thus ruling out the involvement of histamine and prostaglandins. This oscillatory response was completely abolished after the removal of extracellular Ca2+, as well as after Ca2+ channel blockade by diltiazem or nifedipine. Sparteine and quinidine, Ca(2+)-activated K+ channel blockade by diltiazem or nifedipine. Sparteine and quinidine, Ca(2+)-activated K+ channel antagonists, also abolished the oscillation. In contrast, tetraethylammonium and 3,4-diaminopyridine, voltage-dependent K+ channel antagonists, augmented the response. Glibenclamide, an antagonist of the ATP-sensitive K+ channel, had no effect on the rhythmic contractions. These results suggest that the rhythmic contractions observed in rabbit mesenteric arteries after ryanodine treatment were caused by the movement of Ca2+ and K+ across the plasmalemma via the voltage-dependent Ca2+ channel and the Ca(2+)-activated K+ channel, respectively.

Phenylephrine-induced oscillatory contractions in rabbit mesenteric arteries were investigated in vitro. Adrenergic, cholinergic, or histamine antagonists as well as cyclooxygenase and lipoxygenase inhibitors had no effect on this phenylephrine-induced oscillation. The removal of extracellular calcium ions or treatment with a calcium antagonist reduced the amplitude and frequency of the oscillation. Removal of the endothelium or treatment with inhibitors of the synthesis or the target enzyme of endothelium-derived relaxing factor (EDRF) also reduced the amplitude and frequency of the oscillation. In a perfusion bioassay, the perfusate from an endothelium-intact arterial segment induced oscillation of an endothelium-denuded arterial ring recipient. These results suggest that phenylephrine-induced oscillation is mediated by an endothelium-derived factor such as EDRF and depends on the influx of extracellular calcium ions.