Vasoconstriction induced by ouabain in the canine coronary artery: contribution of adrenergic and nonadrenergic responses.
Ouabain, when applied to rings of the left circumflex coronary artery of the dog (which contains both alpha 1-adrenoceptors leading to contraction and beta 1-adrenoceptors leading to relaxation) caused an initial contraction which peaked within 15 minutes and a later secondary increase in tension which peaked within 60 minutes. These contractions were prevented by Ca2+ removal or by verapamil. Adrenergic denervation with 6-hydroxydopamine did not affect the initial contraction. Thus it is due to a nonadrenergic effect of the glycoside. Since the secondary increase in tension was prevented by adrenergic denervation and prazosin, it is likely to be due to norepinephrine released from adrenergic nerves acting on alpha-adrenoceptors. This interpretation was confirmed by the finding that ouabain, after a latent period of about 35 minutes, augmented the output of 3H-norepinephrine from helical strips of the artery previously incubated with tritiated transmitter. In rings contracted with prostaglandin F2 alpha, ouabain reduced beta-adrenergic relaxations caused by isoproterenol or exogenous norepinephrine, but not those caused by sodium nitroprusside. Thus, in this artery, ouabain depresses the responses of the beta-adrenoceptors to the norepinephrine which it releases, thereby permitting the neurotransmitter to cause contraction by activating postjunctional alpha 1-adrenoceptors.
Cooke
J P
JP
Department of Physiology and Biophysics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905.
Shepherd
J T
JT
Vanhoutte
P M
PM
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004837:Epinephrine / Q000502:physiology; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D010042:Ouabain; D009638:Norepinephrine; D004837:Epinephrine