Bradykinin induced sustained anti-adrenergic actions in guinea pig heart muscle involves PKC

OBJECTIVES: Adenosine attenuates the effect of beta-adrenergic stimulation upon contractile force, both when present during beta-adrenergic stimulation and for a period after washout of adenosine. Protein kinase C (PKC) mediates the sustained effect. The present study investigated if bradykinin (500 nM) could induce anti-beta-adrenergic actions. DESIGN: Guinea pig papillary muscles (36.5 degrees C, 1 Hz) were subjected to 15 min exposure to and 20 min washout of bradykinin. Isoproterenol 100 nM was added for 3 min at the end of test exposure and at the end of washout. The PKC-inhibitor bisindolylmaleimide (20 nM) was given to investigate the importance of PKC. RESULTS: Bradykinin significantly reduced the increase in contractile force in response to isoproterenol, both when present and after washout of test substance. Inhibition of PKC abolished the sustained effect, while inhibition of PI3-kinase with wortmannin did not seem to affect the results. CONCLUSIONS: Anti-beta-adrenergic effects of bradykinin on contractile force and action potential duration were demonstrated. PKC was important for the sustained effect on contractile force, but not for the acute effect and the effect on action potential duration.