Role of adenosine in hypoxic alterations of anaphylaxis of isolated guinea pig hearts.
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.
Heller
L J
LJ
Department of Physiology, University of Minnesota, School of Medicine, Duluth 55812.
Trachte
G J
GJ
Regal
J F
JF
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000707:Anaphylaxis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D000941:Antigens / Q000276:immunology; D001283:Atrioventricular Node / Q000503:physiopathology; D003326:Coronary Circulation; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D006632:Histamine / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013931:Thromboxanes / Q000378:metabolism
D000941:Antigens; D013931:Thromboxanes; D007288:Inosine; C031433:8-(4-sulfophenyl)theophylline; D006632:Histamine; D013806:Theophylline; D000241:Adenosine