Effects of felodipine, nifedipine and verapamil on cytosolic Ca2+ and contraction in vascular smooth muscle.
The inhibitory effects of felodipine, nifedipine and verapamil were compared in vascular smooth muscle. In rat aorta, these inhibitors attenuated the high K(+)-induced contraction with a parallel decrease in the cytosolic Ca2+ level ([Ca2+]i). Maximal inhibition was obtained with 10 nM felodipine, 100 nM nifedipine and 10 microM verapamil. The inhibitory effects were antagonized by an increase in external Ca2+ concentration to 6.5 mM and the addition of a Ca2+ channel activator, 100 nM Bay k 8644. These inhibitors also attenuated the contraction induced by norepinephrine although these effects were weaker than those on high K(+)-induced contraction. Furthermore, these inhibitors attenuated the norepinephrine-stimulated [Ca2+]i more strongly than contraction. In contrast, none of these inhibitors inhibited the transient increase in [Ca2+]i and muscle tension induced by norepinephrine in Ca(2+)-free solution and the Ca(2+)-induced contraction in permeabilized smooth muscle. These results suggest that felodipine, nifedipine and verapamil inhibit smooth muscle contraction by inhibiting Ca2+ channels at concentrations which do not change Ca2+ release or Ca2+ sensitivity of contractile elements.
Hagiwara
S
S
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Mitsui
M
M
Karaki
H
H
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015736:Felodipine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D015736:Felodipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine