Adenosine induces prolonged anti-beta-adrenergic effects in guinea-pig papillary muscle.

ABSTRACT

A sustained anti-beta-adrenergic effect of adenosine has been reported. This study was initiated to investigate this topic and especially elucidate the role of protein kinase C (PKC). Contractile force amplitude and action potential duration at 90% repolarization (APD90) were measured in guinea-pig papillary muscles before and after 5 min challenge with 5 nm isoproterenol. Protocols contained 30 min exposure to the test agents adenosine 33 microm (ado), adenosine + PKC-inhibitor bisindolylmaleimide 20 nM (ado + BIM), PKC-activator 1,2-dioctanoyl-sn-glycerol 10 microm (DOG) and alpha-agonist phenylephrine 5 microm (phe). Isoproterenol was given at the end of test exposure and after 15 min washout. Results are mean +/- SEM of percentage-change, P < or = 0.05 considered significant and labelled *. The first isoproterenol challenge significantly increased contractile force (27 +/- 7%*) in the control group. Responses in the test groups were 2 +/- 4 (ado), 1 +/- 5 (ado + BIM), 14 +/- 4* (DOG), 0 +/- 2% (phe). After washout of adenosine, DOG and phenylephrine, isoproterenol induced 3 +/- 8 (ado), 23 +/- 5* (ado + BIM), 13 +/- 5* (DOG), 15 +/- 7% (phe) increase in test groups compared with 22 +/- 5%* increase in contractile force in the control group. After 45 min washout of adenosine the inotropic response was still significantly reduced compared with control (29 +/- 4 vs. 79 +/- 8%*). Isoproterenol stimulation shortened APD90 in controls at both time points (5 +/- 1%* and 4 +/- 1%*), with no significant shortening in test groups. Adenosine induces sustained anti-beta-adrenergic effects on contractile force as well as APD90. A role for PKC in signal transduction is supported with respect to contractile force.