Effect of ouabain on the responses to vasoconstrictor agents in isolated perfused rat tail arteries.
In isolated rat tail arteries perfused with Krebs-Henseleit solution, ouabain, in concentrations of less than 10(-5) M, caused a concentration-dependent, noncompetitive inhibition of the vasoconstrictor response to phenylephrine. Concentrations of 10(-8) and 10(-6) M caused 30 and 61% inhibition, respectively. The inhibition was gradual in onset, with a maximal effect at 45 min. In concentrations greater than 10(-5) M, ouabain caused a parallel shift to the left of the phenylephrine dose-response curve, indicating potentiation. The potentiation was rapid in onset (within 1 min), and was approximately 1.4-fold. The cutoff point between inhibition and potentiation of vasoconstrictors occurred at a ouabain concentration of 10(-5) M. Ouabain-induced potentiation was nonspecific in regard to the vasoconstrictor used. Phenylephrine, clonidine, and serotonin were each potentiated. Potentiation probably resulted from a reduction in the smooth muscle membrane potential as a consequence of inhibition of Na-K ATPase. The mechanism of the inhibitory effect of ouabain on vasoconstrictors was not resolved but may operate via stimulation of Na-K ATPase. The results are consistent with a "partial agonist" action of ouabain on Na-K ATPase.
S J
SJ
Armsworth
J F
JF
Marwood
G S
GS
Stokes
D000818:Animals; D001158:Arteries / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012701:Serotonin; D010042:Ouabain; D003000:Clonidine