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Mechanism of the negative dromotrophic effect of adenosine 5′‐triphosphate in the guinea pig heart in vivo
Author(s) -
Xu Jiang,
Wang Li,
Hurt Carl,
Pelleg Amir
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280318
Subject(s) - adenosine , atropine , propranolol , medicine , chemistry , endocrinology , in vivo , antagonist , guinea pig , adenosine receptor , adenosine a1 receptor , adenosine triphosphate , anesthesia , biology , receptor , agonist , microbiology and biotechnology
To test the hypothesis that the vagus nerve does not play a major mechanistic role in the cardiac electrophysiologic action of adenosine 5′‐triphosphate (ATP), the negative dromotropic actions of the nucleotide and adenosine on atrioventricular (AV) nodal conduction were quantitated in an in vivo guinea pig model. Anesthetized animals were divided into three groups. In group 1, ATP and adenosine (0.1–10.0 μmol/kg, iv) were given at random as a rapid bolus during right atrial pacing (paced cycle length 220–270 msec). This protocol was repeated following the administration of atropine (0.2 mg/kg, iv) followed by propranolol (1 mg/kg, iv). In group 2, ATP and adenosine (1.6 μmol/kg, iv) were given in the absence and presence of the selective A 1 ‐adenosine receptor antagonist, N 6 ‐endonorbornan‐2‐yl‐9‐methyladenine (N‐0861, 30 μmol/kg, iv), and in group 3, ATP and adenosine were given as in group 2 but instead of N‐0861, an adenosine transport blocker, dipyridamole (250 μg/kg, iv), was used. Standard lead I and II electrocardiogram, right atrial, right ventricular, and His bundle electrogram as well as systemic arterial blood pressure were continuously monitored and recorded. AV nodal conduction time was quantitated as AH interval. ATP and adenosine were equipotent in suppressing AV nodal conduction. For example, maximal AH interval following the highest dose of ATP and adenosine was 102 ± 10 and 112 ± 7 msec, respectively. These effects were not significantly altered by either muscarinic cholinergic or β‐adrenergic blockade. Furthermore, N‐0861 attenuated and dipyridamole enhanced the effects of ATP and adenosine similarly. It was concluded that the electrophysiologic action of ATP in the guinea pig AV node in vivo is independent of the vagus nerve and mediated by its degradation to adenosine and the action of the latter on A 1 ‐adenosine receptors. © 1993 Wiley‐Liss, Inc.