Effects of dipyridamole on postischemic vasodilation and extracellular adenosine.
Postischemic vasodilation (PIVD) was studied in pump-perfused dog gracilis muscles. The hemodynamic responses to 1, 3, and 5 min of ischemia were evaluated in the presence and absence of intraarterial infusions of dipyridamole in concentrations that inhibit cellular transport of adenosine. Dipyridamole infusion produced concentration-dependent reductions in vascular resistance and increased the time for 50% recovery (t0.5) in vascular resistance by 39% following 5 min of ischemia. The t0.5 for PIVD was unaffected by dipyridamole following 1 and 3 min of ischemia. Dipyridamole elevated tissue adenosine content two- to three-fold at 1, 3, and 5 min of ischemia compared with saline controls. Intra-arterial infusions of adenosine deaminase along with dipyridamole completely prevented the dipyridamole-induced increase in tissue adenosine, demonstrating that dipyridamole increases extracellular adenosine during muscle ischemia. The significance of these findings is analyzed using a two-compartment model for the distribution of adenosine. The data indicate that a severalfold increase in interstitial adenosine content does not alter PIVD and that the hemodynamic effects of dipyridamole following 5 min of ischemia may be due to some mechanism other than enhanced accumulation of adenosine.
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D004176:Dipyridamole; D000243:Adenosine Deaminase; D000241:Adenosine