Vasoconstrictor responses to the alpha 2-adrenoceptor agonist UK14304 during responses to noradrenaline, phenylephrine, serotonin and vasopressin of the rat tail artery.
In the isolated perfused rat tail artery, the alpha 2-adrenoceptor agonist UK14304 alone did not exert a direct vasoconstrictor action until a concentration of at least 30 microM was reached. However, when administered during the sustained vasoconstrictor response to 1.6 microM vasopressin, UK14304 (1-100 nM) produced additional concentration-dependent increases in perfusion pressure. The vasoconstrictor response to UK14304 in the presence of vasopressin was antagonized by idazoxan (1 microM) but was not affected by prazosin (10 nM), indicating that it was due to activation of alpha 2-adrenoceptors, and it was reduced by diltiazem (10 microM) and abolished when perfusion was done with a Ca2(+)-free solution, suggesting that the effect depends on the influx of Ca2+. UK14304 (50 nM) also produced a further increase in perfusion pressure when given during sustained vasoconstrictor responses to phenylephrine (1 microM) or low concentrations (100 nM) of noradrenaline or serotonin. However, UK14304 did not produce a further increase in perfusion pressure when given during sustained vasoconstrictor responses to higher concentrations (300 nM) of noradrenaline or serotonin: the lack of an additional effect of UK14304 was not due to the primary response to noradrenaline or serotonin being maximal. The findings show that vasoconstrictor responses following activation of alpha 2-adrenoceptors may be uncovered by an increase in vascular tone produced by some agonists.
Xiao
X H
XH
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Rand
M J
MJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D014667:Vasopressins; D010656:Phenylephrine; D012701:Serotonin; D000068438:Brimonidine Tartrate; D004110:Diltiazem; D002118:Calcium; D009638:Norepinephrine