Yumi Katano

The effects of norepinephrine on the release of cyclic AMP by the isolated perfused heart of the guinea pig.

Abstract In the isolated perfused heart preparation of the guinea pig, continuous infusions of norepinephrine in doses of 0.06, 0.2 and 0.6 μg/min resulted in a dose-dependent increase in the heart rate, augmentation of the heart contractility measured as increments of dp/dt max. and an increase in the coronary flow. Simultaneous with these changes, a dose-dependent release of substantial quantities of cyclic AMP into the perfusate was observed, and there was a close moment to moment correlation between the increments of dp/dt max. and the increases in the amount of released cyclic AMP produced by norepinephrine. A linear correlation, though less marked than that described above, was also observed between the positive chronotropic and coronary vasodilatatory effects and the increases in the amount of released cyclic AMP, while there was no dynamic correlation between the tissue cyclic AMP level and the augmentation of the mechanical performances of the heart; Increases in the tissue cyclic AMP level were observed only with the highest dose and were transient and a significant decrease was noted with the lowest dose. The decrease was abolished by phentolamine. It is concluded that cyclic AMP exists in different ntracellular compartments in the heart, only one of which -- comprising a small fraction of the total cellular cyclic AMP, -- is functionally-relevant, and that much of this fraction can pass relatively freely across the cell membrane.