Endogenous adenosine, A1 adenosine receptor, and pertussis toxin sensitive guanine nucleotide binding protein mediate hypoxia induced AV nodal conduction block in guinea pig heart in vivo.
OBJECTIVE
The aim was to study the mechanism of global hypoxia induced atrioventricular (AV) nodal conduction block in vivo using a guinea pig model.


METHODS
Animals subjected to 10 min periods of global hypoxia, induced by decremental changes in O2 content in the inhaled gas mixture, were randomly divided into three groups: group I = control; group II = animals treated with a new selective A1 adenosine receptor antagonist, N0861 (N6-endo-norbornan-2-yl-9-methyladenine); and group III-animals treated with pertussis toxin, an irreversible inhibitor of specific guanine nucleotide binding proteins (G protein).


RESULTS
Progressive incremental hypoxia was associated with progressive AV nodal conduction delay culminating in a complete block. In addition, there was an inverse relationship between the severity of hypoxia and time to AV nodal block. Both N0861 and pertussis toxin treatment significantly reduced the degree of hypoxia induced AV nodal conduction block and delayed its appearance.


CONCLUSIONS
(1) Endogenous adenosine released during acute global hypoxia causes AV nodal conduction block observed under these conditions in the guinea pig heart in vivo; and (2) this action of adenosine in the AV node is mediated by an A1 adenosine receptor and a pertussis toxin sensitive G protein.
Xu
J
J
Likoff Cardiovascular Institute, Hahnemann University, Philadelphia, PA 19102-1192.
Tong
H
H
Wang
L
L
Hurt
C M
CM
Pelleg
A
A
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006327:Heart Block / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D009636:Norbornanes / Q000494:pharmacology; D037342:Pertussis Toxin; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D009636:Norbornanes; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; C073387:N 0861; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000225:Adenine; D000241:Adenosine