Possible beta-adrenoceptor modulating effect of ZK 36 374 a stable analogue of carbacyclin.

Experiments were performed to investigate the nature of the interaction of noradrenaline (NA) and adrenaline (A) with ZK 36 374, a stable analogue of carbacyclin, in spontaneously beating isolated rat right atria and spirally cut rabbit aortic strips. At lower concentrations (below 10(-8) M), ZK 36 374 failed to alter heart rate and contractility but caused an inhibition of both NA effects. At higher concentrations (above 10(-7) M), the compound produced a weak positive chronotropic and inotropic response but did not cause a further decrease in the responses to NA. At the same concentrations propranolol (PR) produced more pronounced inhibition of NA actions. The nature of the inhibition by ZK 36 374 against NA in the rat atria seems to be different from that of PR since the calculated pD2 values of NA were the same for chronotropic and inotropic responses in control experiments and in the presence of PR while the pD2 value of NA for chronotropic response was significantly lower than that for inotropic response in the presence of ZK 36 374. Nicotine partly reversed the inhibitory effect of PR against NA on heart rate which was prevented by ZK 36 374. ZK 36 374 caused a significant potentiation of the contractile response to A but not to NA in rabbit aortic strips. These results suggest that ZK 36 374 interacts with beta-adrenoceptors causing an inhibition on the responses of beta-mediated pharmacological effects of A and NA. These results were also taken as an evidence that PR may partly act through the release of endogenous PGI2.