Summary
Ouabain, when applied to rings of the left ciroumfiex coronary artery of the dog (which contains both alpha1-adrenoceptors leading to contraction and beta1-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 F2α, 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 response of the beta-adrenoceptors to the norepinephrine which it releases, thereby permitting the neurotransmitter to cause contraction by activating postjunctional alpha1-adrenoceptors.
Similar content being viewed by others
References
Lorenz RR, Powis DA, Vanhoutte PM, Shepherd JT. The effects of acetylstrophanthidin and ouabain on the sympathetic adrenergic neuroeffector junction in canine vascular smooth muscle. Circ Res 1980; 47:845–854.
Aarhus LL, Shepherd JT, Tyce GM, et al. Contractions of canine vascular smooth muscle cells caused by ouabain are due to release of norepinephrine from adrenergic nerve endings. Circ Res 1983; 52:501–507.
Brender D, Strong CG, Shepherd JT. Effects of acetyl-strophanthidin on isolated veins of the dog. Circ Res 1970; 26:647–655.
De Mey JG, Claeys M, Vanhoutte PM. Endothelium-dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery. J Pharmacol Exp Ther 1982; 222:166–173.
Mulvany MJ. Effect of electrolyte transport on the response of arteriolar smooth muscle. J Cardiovasc Pharmacol 1984; 6:S82-S87.
Vatner SF, Hintze TH. Mechanism of constriction of large coronary arteries by β-adrenergic receptor blockade. Circ Res 1983; 53:389–400.
Cohen RA, Shepherd JT, Vanhoutte PM. Prejunctional and postjunctional actions of endogenous norepinephrine at the sympathetic neuroeffector junction in canine coronary arteries. Circ Res 1983; 52:16–25.
Furchgott RF, Zawadzki JV. The obligatory smooth muscle by acetylcholine. Nature 1980; 288:373–376.
De Mey, Vanhoutte PM. Role of the intima in cholinergic and puringeric relaxation of isolated canine femoral arteries. J Physiol (Lond) 1981; 316:374–355.
De May JG, Claeys M, Vanhoutte PM. Endothelium-dependent inhibitory effects of acetylcholine, adenosine triphosphate, thrombin and arachidonic acid in the canine femoral artery. J Pharmacol Exp Ther 1982; 222:166–173.
Vanhoutte PM, Leusen I. The reactivity of isolated venous preparations to electrical stimulation. Pflugers Arch 306: 341–353.
Verbeuren TJ, Coen E, Vanhoutte PM. Determination of3H-norepinephrine and its metabolites in superfusate from isolated blood vessels. Arch Int Pharmacodyn Ther 1977; 227:171–174.
Verbeuren TJ, Janssens WJ, Vanhoutte PM. Effect of moderate acidosis on adrenergic neurotransmission in canine saphenous veins. J Pharmacol Exp Ther 1978; 206:105–114.
Verbeuren TJ, Vanhoutte PM. Cocaine and neurol uptake in the canine saphenous vein. Naunyn Schmidebergs Arch Pharmacol 1982; 321:207–212.
Aprigliano O, Hermsmeyer K. In vitro denervation of the portal vein and caudal artery of the rat. J Pharmacol Exp Ther 1976; 198:568–577.
Cohen RA, Shepherd JT, Vanhoutte PM. 5-hydroxy-tryptamine can mediate endothelium-dependent relaxation of coronary arteries. Am J Physiol 1983; 245:H1077-H1080.
Tsuru H, Shigei T. Participation of catecholamine in the digitoxigenin-induced contraction of isolated dog veins. Jpn J Pharmacol 1976; 26:120–122.
Adams RJ, Wallick ET, Asano G, et al. Canine mesenteric artery Na+, K+—ATPase: Vasopressor receptor for digitalis? J Cardiovasc Pharmacol 1983; 5:468–482.
Vanhoutte PM, Lorenz RR. Na+, K+ ATPase inhibitors and the adrenergic neuroeffector interaction in the blood vessel wall. J Cardiovasc Pharmacol 1984; 6:S88-S94.
Vanhoutte PM, Verbeuren TJ, Webb RC. Local modulation of adrenergic neuroeffector interaction in the blood vessel wall. Physiol Rev 1981; 61:151–247.
Rimele TJ, Rooke TW, Aarhus LL, Vanhoutte PM. Alpha-1 adrenoceptors and calcium in isolated canine coronary arteries. J Pharmacol Exp Ther 1983; 226:668–672.
Morales-Aguilera A, Vaughan Williams EM. The effects on cardiac muscle of β-receptor antagonists in relation to their activity as local anesthetic. Br J Pharmacol 1984; 6:S82-S87.
De Mey JG, Vanhoutte PM. Interaction between Na+, K+ exchanges and the direct inhibitory effect of acetylcholine on canine femoral arteries. Circ Res 1980; 46:826–836.
Webb RC, Bohr DF. Relaxation of vascular smooth muscle by isoproterenol dibutyryl-cyclic AMP and theophylline. J Pharmacol Exp Ther 1981; 217:26–35.
Scheid CR, Honeyman TW, Fay FS. Mechanism of β-adrenergic relaxation of smooth muscle. Nature 1979; 277:32–36.
Balcon R, Hoy J, Sowton E. Haemodynamic infarction. Br Heart J 1968; 30:373–376.
Crawford MH, LeWinter MM, O'Rourke RA, et al. Combined propranolol and digoxin therapy in angina pectoris. Ann Intern Med 1975; 83:449–455.
Vatner SF, Higgins CB, Franklin D, Braunwald W. Effects of a digitalis glycoside on coronary and systemic dynamics in conscoius dog. Circ Res 1971; 28:470–479.
Garan H, Smith TW, Powell WJ. The central nervous system as a site of action for the coronary vasoconstrictor-effect of digoxin. J Clin Invest 1974; 54:1365–1372.
Tanz TD, Russell NJ. Mechanism of cardiac glycosides-induced toxicity: Physiology, biochemistry and electron microscopy. Fed Proc 1983; 42:2470–2474.
Ferrer MI, Bradley SE, Wheeler HO, et al. The effects of digoxin in the splanchnic circulation in ventricular failure. Circulation 1966; 32:524–537.
Bowerman RE, Steinmetz EF, Schwarten DE, et al. Reversal of digitalis-induced vasospasm by sodium nitroprusside. Arch Intern Med 1982; 142:403–405.
Demetos H, Rahimtoola SH, McAnulty JH, Porter GA. Effects of ouabain on coronary and systemic vascular resistance and myocardiol oxygen consumption in patients without heart failure. Am J Cardiol 1978; 41:88–93.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cooke, J.P., Shepherd, J.T. & Vanhoutte, P.M. Vasoconstriction induced by ouabain in the canine coronary artery: Contribution of adrenergic and nonadrenergic responses. Cardiovasc Drug Ther 2, 255–263 (1988). https://doi.org/10.1007/BF00051242
Issue Date:
DOI: https://doi.org/10.1007/BF00051242