The Positive Inotropic Action of Isoprenaline Is Associated With the Release of Noradrenaline From Rabbit, Guinea‐pig and Rat Atria

The actions of isoprenaline (1 microM) were investigated in spontaneously beating isolated paired atria from rabbits, guinea-pigs and rats and in paced left atria from rabbits and rats. Isoprenaline, when applied for a 10 min period to paired atrial from rabbits, guinea-pigs and rats, produced a short-lived release of noradrenaline which appeared to be associated with the positive inotropic actions, rather than with the positive chronotropic actions. Exposures of 3 min to isoprenaline in paired atria in the three species produced increases in force and release of noradrenaline (% of tissue content) in the order: rabbit greater than guinea-pig greater than rat. The increases in rate did not differ between species. Rat atria had the highest resting rates followed by guinea-pig and rabbit atria. In rabbit left atrial preparations which were electrically paced at resting rates of approximately 61, 158 and 334 beats per min there were progressive decreases in release of noradrenaline and positive inotropic actions produced by isoprenaline with increasing rates of pacing. In rat left atrial preparations which were electrically paced at a slower rate, which was similar to that of rabbit paired atria, a greater release of noradrenaline associated with a greater positive inotropic effect was induced by isoprenaline than in rat paired atria. In rabbit paced left atria, an increase in pacing frequency alone produced small increases in force and release of noradrenaline. Verapamil (1 microM) significantly reduced the positive inotropic effect and release of noradrenaline induced by isoprenaline without affecting the positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)