AJP - Heart and Circulatory Physiology, Vol 257, Issue 5 1378-H1388, Copyright © 1989 by American Physiological Society
Role of adenosine in hypoxic alterations of anaphylaxis of isolated guinea pig hearts
L. J. Heller, G. J. Trachte and J. F. Regal
Department of Physiology, University of Minnesota, School of Medicine, Duluth 55812.
Previous studies suggest that high levels of adenosine may enhance
histamine release and contribute to atrioventricular (AV) nodal conduction
arrhythmias during anaphylaxis of isolated guinea pig hearts. To determine
whether elevations in endogenous adenosine evoked by hypoxic conditions
have similar effects, isolated hearts of guinea pigs passively sensitized
by intracardiac injection were perfused with solutions equilibrated with
95% O2 (normoxia) or 30% O2 (hypoxia). When compared with normoxia, hypoxia
before antigen challenge increased adenosine release, decreased vascular
resistance, and prolonged P-R intervals, whereas hypoxia during anaphylaxis
potentiated the increase in adenosine release, attenuated the increases in
vascular resistance and atrial rate, and increased the occurrence of
conduction arrhythmias without altering the antigen-induced release of
either histamine or thromboxane. Addition of the adenosine receptor
antagonist 8-(4-sulfophenyl)theophylline (SP-T) to the hypoxic perfusate
significantly decreased antigen-induced release of histamine and
thromboxane. These data indicate that 1) hypoxia-induced depression of
antigen-induced mediator release may be counteracted by the stimulatory
effect of the increased adenosine induced by hypoxia, and 2) under hypoxic
conditions, adenosine's negative dromotropic, chronotropic, and
vasodilatory effects may influence the anaphylactic reaction.
