Effect of Pinacidil on the Contraction of Rabbit Carotid Artery

ABSTRACT

The effect of pinacidil, a K+ channel opener, on the contraction of rabbit carotid artery was investigated by using muscle contraction and Ca2= uptake experiments. Pinacidil reduced phenylephrine-induced contraction by dose dependent manner, which was antagonized by glibenclamide, a blocker of the ATP sensitive K+ channel. Phenylephrine-induced tonic contraction was more reduced by pinacidil than its phasic contraction. In the effect of pinacidil on the Ca2+ uptake of rabbit carotid artery, pinacidil decreased it at the resting state of tissue, dose-dependently. Phenylephrine-induced stimulation of Ca2+ uptake was also reduced by pinacidil. Pinacidil 10micrometer reduced high potassium-induced contraction, which was not reversed by glybenclamide 10micrometer. Threshold concentration of K+ increased by pinacidil pretreatment. Phorbol 12, 13-dibutyrate, an activator of protein kinase C, induced sustained contraction of rabbit carotid artery, which was reduced by pinacidil but not antagonized by glibenclamide. In Ca2+-free buffer, pinacidil also decreased phorbol 12, 13-dibutyrate-induced contraction. These results indicate that pinacidil reduces Ca2+ uptake of vascular smooth muscle by stimulation of K+ channel which could be antagonized by glibenclamide, and another mechanism of vasorelaxation which could not be antagonized by glibenclamide. It was indecated that pinacidil affects the contaction of smooth muscle by the inhibition of protein kinase C.