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


METHODS
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.
Arvola
Laila
L
Kirkenes Hospital, Kirkenes, and Department of Medical Physiology, Faculty of Medicine, University of Tromsø, Norway.
Bertelsen
Geir
G
Ytrehus
Kirsti
K
D000200:Action Potentials / Q000187:drug effects*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009206:Myocardium; D011493:Protein Kinase C; D014665:Vasodilator Agents / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D014665:Vasodilator Agents; D011493:Protein Kinase C; D007545:Isoproterenol; D001920:Bradykinin