ENDOTHELIUM-DEPENDENT AND ENDOTHELIUM-INDEPENDENT VASODILATION OF ISOLATED RAT AORTA INDUCED BY CAFFEINE

Caffeine (10(-4)-10(-3) M) induced concentration-dependent relaxations of phenylephrine-precontracted rat aortic rings with endothelium. End othelial denudation significantly, but only partially, attenuated caff eine-induced relaxation. Pretreatment with N-G-nitro-L-arginine, oxyhe moglobin, and methylene blue attenuated the relaxations to an extent s imilar to endothelial denudation. Guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) contents of ao rtic strips with endothelium increased significantly after exposure to caffeine (10(-3) M). Endothelial denudation attenuated caffeine-induc ed cGMP increase. Pretreatment with ryanodine (2 x 10(-5) M), which ha s been shown to combine with receptors on endoplasmic reticulum (ER) o f endothelium, attenuated caffeine-induced relaxation and cGMP content increase of rings with endothelium. Pretreatment with caffeine potent iated sodium nitroprusside-induced relaxations and cGMP increase of ri ngs without endothelium. These results demonstrated that caffeine-indu ced relaxation comprises two components. In the endothelium-dependent mechanism, caffeine promotes nitric oxide synthesis in endothelium by release of Ca2+ from ER through a ryanodine-sensitive Ca2+ channel, an d the suppression of cGMP degradation also contributes to the relaxati on. In the endothelium-independent mechanism, caffeine acts as a 3',5' -cyclic-nucleotide phosphodiesterase inhibitor.