Amplification of alpha adrenergic vasoconstriction in canine isolated mesenteric artery and vein.
The interactions between UK-14304 and other vasoconstrictor agents were investigated using isolated canine mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, exposure to UK-14304 caused a small contraction, producing 8% of the KCl maximal response. In the presence of either 20 mM KCl or 10(-9) M endothelin-1, which had small contractile effects, UK-14304 produced a biphasic concentration-response curve; 10(-7) M rauwolscine inhibited the responses to low concentrations of UK-14304 and 10(-7) M prazosin blocked the responses to high concentrations of UK-14304. In the presence of 10(-8) M Bay K 8644, UK-14304 elicited a monophasic concentration-dependent contraction that was antagonized by 10(-7) M prazosin, not by 10(-7) M rauwolscine. In the mesenteric vein, UK-14304 elicited concentration-dependent contractions, producing 63% of the KCl maximal response. The lower part of the biphasic concentration-response curve was inhibited by 10(-7) M rauwolscine and the upper part of the curve was antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, 10(-11) M endothelin-1 or 10(-9) M Bay K 8644, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to UK-14304 primarily at concentrations lower than 10(-6) M. The enhancement of responses were prazosin (10(-7) M)-resistant and rauwolscine (10(-7) M)-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimamoto
H
H
Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Bourreau
J P
JP
Kwan
C Y
CY
Daniel
E E
EE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D016232:Endothelins; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D011224:Prazosin