Pharmacological properties of alpha 1-adrenoceptor-mediated vasoconstrictions in dog and monkey lingual arteries: evidence for subtypes of alpha 1-adrenoceptors.
We examined whether alpha 1-adrenoceptor-mediated vasoconstrictions were due to extra- or intracellular Ca2+ movements, and whether they were subdivided into alpha 1-adrenoceptor subtypes in dog and monkey lingual arteries. The NE-induced vasoconstriction in dog lingual arteries was mostly dependent on Ca2+ influx from the extracellular space, since it was readily blocked by a Ca2+ entry blocker, diltiazem, and the NE-induced response was attenuated approximately 90% in Ca(2+)-free solution. On the other hand, in monkey lingual arteries, diltiazem failed to depress the NE-induced dose-response curve, and the response was attenuated only about 60% in Ca(2+)-free solution. The vasoconstrictor response to 10mg caffeine in normal KHS was almost the same as that to 1 micrograms NE in Ca(2+)-free solution in both kinds of arteries, suggesting that alpha 1-adrenoceptor-mediating vasoconstrictions require a different number of sources of Ca2+ in different blood vessels. Pretreatment of preparations with CEC (an alpha 1B-antagonist) significantly suppressed and shifted the dose-response curve for NE to the right in monkey lingual arteries, but it had no significant effect in dog lingual arteries. However, WB4101 (an alpha 1A-antagonist) showed almost the same potency in blocking vasoconstrictor responses as bunazosin in both kinds of arteries (the pA2 values were not significantly different). Moreover, responses to ME (an alpha 1A-agonist) were blocked by diltiazem as well as by bunazosin and WB4101, while CEC had no blocking effect on ME-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Skrbic
R
R
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Chiba
S
S
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008251:Macaca; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000145:classification / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D014059:Tongue / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D004146:Dioxanes; D011941:Receptors, Adrenergic; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D004110:Diltiazem; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine