The effects of BAY-K-8644 on the contraction of cat middle cerebral and femoral arteries.
The effects of BAY-K-8644 on the reactivity of cylindrical segments of cat middle cerebral and femoral arteries were studied. BAY-K-8644 induced dose-dependent contractile responses in cerebral arteries up to 10(-6) M; higher concentrations tended to cause relaxation of the segments. The dihydropyridine elicited contractions in femoral arteries only when these vessels were previously exposed to 15 mM K+. Nifedipine (3 X 10(-7) M) produced a parallel shift to the right of the dose-response curve to BAY-K-8644, whereas 5 X 10(-6)M verapamil markedly reduced the responses evoked by all concentrations of this drug. The removal of Ca2+ from the medium abolished the response evoked by the Ca2+-channel activator at 10(-7) M in both kinds of arteries. Under these conditions Ca2+ addition induced vasoconstriction, which was blocked by nifedipine (3 X 10(-7) M). Preincubation of femoral arteries with 10(-7) M BAY-K-8644 potentiated the effects evoked by 25, 50, 75 and 125 mM K+, but did not modify those produced by 10(-5) M noradrenaline. Nifedipine (10(-7) M and 3 X 10(-7) M) blocked the potentiation caused by this drug in a dose-dependent manner. Both the increase of the response elicited by BAY-K-8644 and the inhibitory effects of nifedipine were greater at 25 mM K+ than at 125 mM. These results suggest that BAY-K-8644 facilitates Ca2+ influx into smooth muscle through Ca2+ channels that are possibly voltage sensitive and the voltage independence of the drug-induced contractions in cerebral arteries.
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M
Salaices
J
J
Marin
C F
CF
Sanchez-Ferrer
J
J
Reviriego
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002118:Calcium / Q000502:physiology; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium