AN ENDOTHELIUM-DEPENDENT CONTRACTION IN CANINE MESENTERIC-ARTERY CAUSED BY CAFFEINE

1 We examined whether or not caffeine caused an endothelium-dependent contraction (EDC) in canine mesenteric artery and whether the endothel ium-dependent contracting factors (EDCF) were arachidonic acid metabol ites. 2 Caffeine (1, 3 and 10mM) caused a transient contraction in end othelium-intact arterial strips. Removal of the endothelium significan tly attenuated the caffeine (1 and 3 mM)-induced contraction. 3 Caffei ne (1 mM)-induced EDC was not affected by quinacrine and manoalide (ph ospholipase Al inhibitors), indomethacin and aspirin (cyclo-oxygenase inhibitors), ONO-3078 and S-1452 (thromboxane Az antagonists) or AA-86 1 and TMK-777 (lipoxygenase inhibitors). 4 Caffeine (1 mM)-induced EDC was also unaffected by 50-235 (an endothelin A receptor antagonist). In addition, catalase combined treatment with superoxide dismutase, or allopurinol (antioxidant) did not affect the EDC. 5 Gro-PIP and NCDC (phospholipase C inhibitors) did not affect the caffeine-induced EDC. However, wortmannin (a phospholipase D inhibitor) and staurosporine (a protein kinase C inhibitor) attenuated the caffeine-induced EDC. 6 Th e present experiments demonstrate that caffeine causes an EDC in canin e mesenteric artery and suggest that the EDCF mediating this response is probably not arachidonic acid metabolites, endothelin or superoxide . Instead, caffeine-induced EDC may be due to activation of the phosph olipase D pathway.