This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Waxman, M. B. Articles by Asta, J. A. Search for Related Content PubMed PubMed Citation Articles by Waxman, M. B. Articles by Asta, J. A.

(Circulation. 1998;98:1228-1235.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Role of Adenosine Receptors in the Paradoxic Bradycardia Response of Rats to Inferior Vena Cava Occlusion During an Infusion of Isoproterenol

Menashe B. Waxman, MD, FRCP(C); ; John A. Asta

From the Department of Medicine of the University of Toronto and the Division of Cardiology of the Toronto Hospital, Ontario, Canada.

Background—In susceptible humans, vasodepressor reactions are induced by restriction of venous return (upright tilting) and administration of isoproterenol. Because paradoxic bradycardia is a major manifestation of vasodepressor reactions, and allowing for extrapolation between paradoxic bradycardia in rats and vasodepressor reactions, we examined whether adenosine receptors mediate the paradoxic bradycardia reaction.

Methods and Results—Paradoxic bradycardia was induced in rats by inferior vena cava occlusion during an isoproterenol infusion. We studied whether dipyridamole, an adenosine transport inhibitor, and aminophylline (nonselective) or DPCPX (selective) A₁ antagonists augmented or inhibited paradoxic bradycardia, respectively, during inferior vena cava occlusion. The maximum changes in R-R during 60 seconds of inferior vena cava occlusion were that (1) in control, the rate accelerated (R-R, -9.7±0.8 ms, P<0.001); (2) during isoproterenol (0.8 µg · min^-1), paradoxic bradycardia occurred (R-R, +92.0±32.0 ms, P<0.001); (3) during isoproterenol but after dipyridamole, paradoxic bradycardia occurred at a much lower dose of isoproterenol (0.2 µg · min^-1), and the magnitude was increased at all doses (at 0.8 µg · min^-1 isoproterenol, R-R, +195.6±27.6 ms, P<0.001 versus isoproterenol alone, R-R, +92.0±32 ms); (4) during isoproterenol and dipyridamole, atropine did not block paradoxic bradycardia, but cervical vagotomy inhibited paradoxic bradycardia (R-R, +5.6±1.8 ms, P<0.001 compared with isoproterenol and dipyridamole alone); and (5) during isoproterenol alone, aminophylline or DPCPX blocked paradoxic bradycardia (R-R, -5.4±1.0 ms, and R-R, -2.6±0.5 ms, respectively, each P<0.001 compared with isoproterenol alone).

Conclusions—The adenosine A₁ receptor mediates the paradoxic bradycardia reflex during inferior vena cava occlusion in the face of isoproterenol via vagal afferents.

Key Words: heart rate • adenosine • receptors • reflex

This article has been cited by other articles:

				S. W. Parry, S. Nath, J. P. Bourke, R. S. Bexton, and R. A. Kenny Adenosine test in the diagnosis of unexplained syncope: marker of conducting tissue disease or neurally mediated syncope? Eur. Heart J., June 2, 2006; 27(12): 1396 - 1400. [Abstract] [Full Text] [PDF]