Abstract
The effect of vesnarinone (OPC-8212), an orally active positive inotropic agent was studied in tracheal muscle isolated from guinea pigs, and the mechanism of its action was analyzed. Vesnarinone (10-6 -10-4 M) caused a concentration-dependent relaxation of tracheal muscle pre-contracted by 10-4 M histamine. The potency of the relaxing effect of vesnarinone was greater than that of theophylline; the pD2 values for vesnarinone and theophylline were 4.9 and 4.5, respectively. Vesnarinone reduced the high-K+-induced contracture of depolarized tracheal muscle non-competitively (pD''2=3.7). Vesnarinone at the low concentration of 3 × 10-6 M shifted the concentration-response curve for isoproterenol in a parallel fashion to the left. Vesnarinone additively acted on the relaxing effect of isobutyl methyl xanthine. Propranolol (10-5 M) and reserpine pre-treatment (5 mg/kg, i.p., 24 hr) had no effect on the relaxing effect of vesnarinone. These results suggested that vesnarinone elevated the intracellular cyclic AMP level via phosphodiesterase inhibition, resulting in the tracheal muscle relaxation.
