The selective potentiation of noradrenaline-induced tone by Bay K 8644 in the rabbit basilar artery.
A number of studies indicate that relative to the maximal tone possible, for example, to histamine, noradrenaline produces only weak contractile responses in the rabbit basilar artery. Various factors, including a limited number of alpha-adrenoceptors, have been proposed to account for the reduced response to noradrenaline. We examined the effect of the Ca2+-channel activator, Bay K 8644 (0.1 and 1.0 nM) on dose-response curves to noradrenaline, histamine, calcium (Ca2+) and potassium (K+) in ring preparations of rabbit basilar artery and central ear artery. These concentrations of Bay K 8644 (0.1 and 1.0 nM) increased the magnitude of tension developed by noradrenaline (contractility) in the basilar artery, but did not alter its sensitivity (ED50) to the adrenergic vasoconstrictor. Bay K 8644 (0.1 and 1.0 nM) did not alter the contractility or sensitivity to histamine or K+ of the rabbit basilar artery. When dose-response curves to Ca2+ were made in K+-depolarized rabbit basilar artery rings, Bay K 8644 (0.1 and 1.0 nM) dose-dependently augmented tone generated by readmission of Ca2+. Bay K 8644 (0.1 and 1.0 nM) did not alter responses to noradrenaline, histamine, or K+ in rabbit central ear artery preparations. These results are compatible with a voltage-dependent mechanism of action of Bay K 8644 in the rabbit basilar artery, which may be partially depolarized in the resting state. We propose that in addition to other factors, the contractile response of rabbit basilar arteries is limited by a weak or inefficient coupling of alpha-adrenoceptors to Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Laher
I
I
Department of Pharmacology, University of Vermont, Burlington 05405.
Germann
P
P
Dowd
A L
AL
Bevan
J A
JA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits
D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006632:Histamine; D009638:Norepinephrine