Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity

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Abstract
In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or CaCl2 (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of cyclic AMP (cAMP). Prolonged prostaglandin E2 (PGE2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+ were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of PGE2 were also observed in Dx-treated hearts, even though the cardiostimulating effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents.