Endothelium-dependent and -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. Endothelial denudation significantly, but only partially, attenuated caffeine-induced relaxation. Pretreatment with NG-nitro-L-arginine, oxyhemoglobin, and methylene blue attenuated the relaxations to an extent similar to endothelial denudation. Guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) contents of aortic strips with endothelium increased significantly after exposure to caffeine (10(-3) M). Endothelial denudation attenuated caffeine-induced cGMP increase. Pretreatment with ryanodine (2 x 10(-5) M), which has been shown to combine with receptors on endoplasmic reticulum (ER) of endothelium, attenuated caffeine-induced relaxation and cGMP content increase of rings with endothelium. Pretreatment with caffeine potentiated sodium nitroprusside-induced relaxations and cGMP increase of rings without endothelium. These results demonstrated that caffeine-induced 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, and the suppression of cGMP degradation also contributes to the relaxation. In the endothelium-independent mechanism, caffeine acts as a 3',5'-cyclic-nucleotide phosphodiesterase inhibitor.
Hatano
Y
Y
Department of Anesthesiology, Wakayama Medical College, Japan.
Mizumoto
K
K
Yoshiyama
T
T
Yamamoto
M
M
Iranami
H
H
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002110:Caffeine; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D012433:Ryanodine; D009599:Nitroprusside; D002110:Caffeine; D000242:Cyclic AMP; D006152:Cyclic GMP