INOTROPIC AND CHRONOTROPIC EFFECTS OF KRN2391, A NOVEL VASODILATOR, ON ISOLATED GUINEA-PIG ATRIA

The chronotropic and inotropic effects of KRN2391, a novel vasodilator , were compared with those of cromakalim and nicorandil in isolated gu inea-pig right and left atria. Negative chronotropic effects of KRN239 1, cromakalim and nicorandil were observed at concentrations of 3 x 10 (-5) M, 10(-6) M, 3 x 10(-3) M and higher, respectively. KRN2391 and c romakalim also produced negative inotropic effects at 3 x 10(-5) M and higher. Nicorandil elicited a negative inotropic action at 10(-4) M a nd higher. When -log EC50 values for three drugs were compared, the ra nk order of potency for the negative chronotropic and inotropic effect s was KRN2391 > cromakalim > nicorandil. The negative chronotropic and inotropic effects of KRN2391, cromakalim and nicorandil were markedly inhibited by glibenclamide, a pharmacological antagonist of K+ channe l opener. These results suggest that the direct effect of KRN2391 as w ell as cromakalim and nicorandil on cardiac function is due to activat ion of glibenclamide-sensitive K+ channels.