Abstract
The effects of acetylcholine chloride (ACh) on cardiac contractile force and on myocardial levels of guanosine 3',5'-monophosphate (cGMP) and adenosine 3',5'-monophosphate (cAMP) were studied in spontaneously beating and electrically driven isolated perfused rat hearts. Perfusion of spontaneously beating hearts with Tyrode's solution containing ACh (7.4 x 10-8 M) produced significant decreases in contractile force and heart rate as well as a significant elevation in myocardial cGMP levels. Excellent correlations were obtained between the changes in the concentrations of cGMP and the effects of ACh on heart rate and force of contraction. Myocardial levels of cAMP were decreased by ACh, but this change was not correlated well with either changes in heart rate on contractile force produced by this agent. In electrically driven hearts cGMP levels were increased by ACh infusion (7.4 x 10-8 M), as in the case of the spontaneously beating hearts, and this change was well correlated with the decrease in contractile force. In electrically driven hearts, as in the spontaneously beating preparation, the correlation between reduced cAMP levels and contractile force was not as good as that between elevated cGMP levels and reduced contractile force. The results of the present study suggest that increased intracellular levels of cGMP produced by ACh may be involved in the mediation of the negative inotropic effect of this agent in the isolated perfused rat heart. Furthermore, such increases in cGMP concentrations may be more important than decreases in concentrations of cardiac cAMP with respect to the mediation of this negative inotropic effect.
Footnotes
- Received July 5, 1972.
- Accepted September 19, 1972.
- © 1973 by The Williams & Wilkins Company
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