![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
HF Clemo, A Bourassa, J Linden and L Belardinelli
Adenosine has been shown to have a negative dromotropic effect and has been implicated in mediating atrioventricular conduction disturbances induced by hypoxia. This study was designed to determine the ability of various alkylxanthines including two novel derivatives, i.e., BW A533U and BW A1433U, to 1) attenuate adenosine- and hypoxia-induced atrial to His bundle (AH) interval prolongation, 2) compete for binding of 125I- aminobenzyladenosine to ventricular membranes and 3) inhibit myocardial phosphodiesterase. In normoxic isolated perfused hearts (n = 20) instrumented for measurement of atrioventricular conduction time and left ventricular pressure, BW A1433U (0.1 microM) or BW A533U (5 microM) attenuated AH interval prolongation induced by adenosine (5 microM) by 90%, but neither xanthine derivative attenuated the AH interval prolongation induced by acetylcholine (0.11 microM), digoxin (0.91 microM) or D600 (1.3 microM). In four additional hearts, BW A1433U at concentrations of up to 10 microM had no effect on left ventricular pressure or AH interval. BW A1433 or BW A533U (50 microM) inhibited myocardial cyclic AMP phosphodiesterase by only 11.5 +/- 1.6 and 26.6 +/- 2.6%, respectively. Schild analysis of adenosine concentration-response curves obtained in the absence and presence of BW A533U and BW A1433U (n = 14) yielded pA2 values of (mean +/- S.E.M.) 6.32 +/- 0.10 and 7.70 +/- 0.08, respectively. pKd values for BW A533U and BW A1433U binding to adenosine receptors on ventricular membranes were 6.36 and 6.94, respectively. In a separate series of 19 hearts, BW A533U and BW A1433U were shown to attenuate hypoxia-induced AH interval prolongation.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  R. Rubio and G. Ceballos Sole activation of three luminal adenosine receptor subtypes in different parts of coronary vasculature Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H204 - H214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Xu, D. A. Berkich, G. H. Crist, and K. F. LaNoue A1 adenosine receptor antagonism improves glucose tolerance in Zucker rats Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E271 - E279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Patil, J. E. Kaplan, and F. L. Minnear Protein, not adenosine or adenine nucleotides, mediates platelet decrease in endothelial permeability Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2304 - H2311. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
