AJP - Heart and Circulatory Physiology, Vol 248, Issue 6 907-H913, Copyright © 1985 by American Physiological Society
Inhibition of rat ventricular automaticity by adenosine
L. J. Heller and R. A. Olsson
This study was designed to characterize adenosine's negative chronotropic
effect on ventricular pacemakers. The spontaneous beating rate of isolated,
isovolumic rat ventricular preparations perfused with Krebs-Henseleit
solution decreased as the adenosine concentration was increased [log M
effective concentration 50% (EC50) = -5.22 +/- 0.17]. The lack of effect of
propranolol or atropine on this adenosine response eliminates the
involvement of endogenous neurotransmitters. Support for the involvement of
an external cell surface receptor was provided by findings that
theophylline and 8-(4-sulfophenyl)theophylline, an analogue thought to act
solely at the cell surface, significantly increased the adenosine log M
EC50 to -3.94 +/- 0.22 and -3.61 +/- 0.22, respectively. An increase in
spontaneous beating rate induced by theophylline, but not by its analogue,
was blocked by the addition of propranolol. The relative chronotropic
potency of the adenosine analogues R-PIA, S-PIA, and NECA suggests that the
cell surface receptors may be of the Ri type. The negative chronotropic
effects of adenosine and its analogues occurred at concentrations that had
no effect on the developed pressure of the paced preparation.
Electrocardiographic evaluations indicate that at high agonist
concentrations, there was an abrupt alteration in electrical properties of
the preparation, which could be blocked by theophylline and its analogue.
