Pharmacological characterization of alpha1-adrenoceptors in mouse isolated femoral small arteries.
Arteries were isolated from male DBA/2 mice and mounted on a small vessel wire myograph for isometric recording. Responses to exogenous noradrenaline were inhibited with high affinity by prazosin (pKB, 9.3) and 5-methyl-urapidil (pKB, 9.2) and with low affinity by 8-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378) (pA(2), 6.7). Chloroethylclonidine (10 microM) produced only a small reduction in the maximum response to noradrenaline. Responses to electrical field stimulation were also inhibited with high affinity by prazosin (pIC50, 9.3-9.5) and 5-methyl-urapidil (pIC50, 8.0-8.3). Responses were sensitive to BMY 7378 at low frequencies of stimulation (pIC50 at 2 Hz, 8.2) but not at high frequencies (pIC50 at 20 Hz, 6.5). In conclusion, contractions to exogenous and endogenous noradrenaline in mouse femoral small arteries are mediated mainly by alpha1A-adrenoceptors. alpha1D-adrenoceptors are not involved in responses to exogenous noradrenaline but appear to be activated by neurally released noradrenaline at a low frequency of stimulation.
Zacharia
Joseph
J
Department of Biological and Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, Scotland, UK.
Hillier
Chris
C
Macdonald
Allan
A
D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005263:Femoral Artery / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C547714:Adra1a protein, mouse; C547717:Adra1b protein, mouse; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; C057446:5-methylurapidil; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin