The bovine aortic endothelial cell line GM-7373 was used to analyse whether dipyridamole could affect gap junction coupling of endothelial cells. Scrape loading/ dye transfer technique revealed that a cell treatment with dipyridamole (1-100 mM) increased the gap junction coupling in concentration dependent manner. Further we found that while forskolin or 8-Br-cAMP increased the gap junction coupling similar to dipyridamole, dibutyryl cGMP did no affect the gap junction coupling of the GM-7373 endothelial cells. Additionally, pharmacological inhibition of PKA with H-89 or Rp-cAMPs antagonised the effect of dipyridamole on gap junction coupling. We propose that dipyridamole related increase of gap junction coupling in endothelial cells is mediated by a cAMP/PKA dependent phosphorylation mechanism. This dipyridamole related modulation of gap junction coupling could be involved in the positive effect of the drug in stroke prevention and treatment. Moreover, we show that gap junction coupling represent a suitable pharmacological target for treatment of cardiovascular diseases.