Endothelium-dependent and independent vasodilation of isolated rat
aorta induced by caffeine.
Hatano, Yoshio, Kazuhiro Mizumoto, Takeshi Yoshiyama, Manabu Yamamoto,
and Hiroshi Iranami.
Department of Anesthesiology, Wakayama Medical College, 7-ban-cho
27, Wakayama 640, Japan; and Department of Anesthesiology, Kyoto
University Hospital, sakyo-ku, Kyoto 606-61, Japan
APStracts 2:0242H, 1995.
Caffeine (10-4 to 10-3 M) induced concentration-dependent relaxations
of phenylephrine-precontracted rat aortic rings with endothelium.
Endothelial denudation attenuated caffeine-induced relaxation
significantly, but only partially. Pretreatment with NG-nitro-L
-arginine, oxyhemoglobin and methylene blue attenuated the relaxations
to a similar extent as endothelial denudation. Cyclic GMP and cyclic
AMP contents of aortic strips with endothelium increased
significantly following exposure to caffeine (10-3 M). Endothelial
denudation attenuated caffeine-induced cyclic GMP increase.
Pretreatment with ryanodine (2X10-5 M), which has been shown to
combine with receptors on endoplasmic reticulum (ER) of endothelium,
attenuated caffeine-induced relaxation and cyclic GMP content
increase of rings with endothelium. Pretreatment with caffeine
potentiated sodium nitroprusside-induced relaxations and cyclic GMP
increase of rings without endothelium. These results demonstrated
that caffeine-induced relaxation comprises two components. In
endothelium-dependent mechanism, caffeine promotes nitric oxide
synthesis in endothelium by release Ca2+ from ER through ryanodine
-sensitive Ca2+ channel and the suppression of cyclic GMP degradation
also contributes to the relaxation. In endothelium-independent
mechanism, caffeine acts as a cyclic AMP phosphodiesterase inhibitor.
Received 8 August 1994; accepted in final form 1 June 1995.
APS Manuscript Number H703-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.