Pharmacological natures of caffeine-induced endothelium-dependent and -independent contraction in canine mesenteric artery.
The present experiments were carried out to elucidate whether pharmacological nature of caffeine (1 mM)-induced endothelium-dependent contraction (EDC) is different from that of caffeine (10 mM)-induced endothelium-independent contraction (EIC) in canine mesenteric artery. Caffeine (1 mM)-induced EDC was abolished when arterial strips were incubated in Ca(++)-free medium for 20 min, but EIC was not abolished. EGTA and EDTA (0.5 and 1 mM) attenuated the EDC, and at the concentration of 2.5 mM completely abolished the EDC. Nifedipine (10(-6) and 3 x 10(-6) M), diltiazem (10(-6) M) and verapamil (10(-6) M) did not affect the caffeine (1 mM)-induced EDC. Lemakalim (10(-8), 3 x 10(-8) and 10(-7) M) attenuated the caffeine (1 mM)-induced EDC in a concentration-dependent manner. Lemakalim (10(-7) M) nearly abolished the EDC. The inhibitory effect of lemakalim (10(-7) M) on the EDC was antagonized in the presence of glibenclamide (3 x 10(-6) M). In contrast, caffeine (10 mM)-induced EIC was resistant to lemakalim at higher concentration (3 x 10(-7) M). Forskolin (10(-7), 3 x 10(-7) and 10(-6) M) significantly attenuated both the caffeine (1 mM)-induced EDC and caffeine (10 mM)-induced EIC. The inhibitory effect of forskolin on the EDC was augmented in the presence of rolipram (10(-6) M). Nitroglycerin (10(-5) M) attenuated significantly caffeine-induced both EDC and EIC. The inhibitory effect of nitroglycerin on the EDC was augmented in the presence of zaprinast (10(-5) M). The present experiments demonstrate that caffeine-induced EDC is due to nifedipine-resistant and lemakalim-sensitive Ca++ mobilization and the EIC is due to both nifedipine- and lemakalim-resistant Ca++ mobilization in canine mesenteric artery.
Jino
H
H
Pharmacology Division, Kyoto University, Japan.
Kurahashi
K
K
Usui
H
H
Shirahase
H
H
Nakata
Y
Y
Shimizu
Y
Y
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D019806:Cromakalim; D004285:Dogs; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D005576:Colforsin; D002110:Caffeine; D004533:Egtazic Acid; D004492:Edetic Acid; D000262:Adenylyl Cyclases; D005996:Nitroglycerin; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium