Mechanism of canine coronary artery relaxation by monensin

H. L. Anderson, R. J. Winquist, R Clinton Webb, D. F. Bohr

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Abstract

Monensin is a monocarboxylic sodium ionophore which causes increased myocardial contractility and increased coronary blood flow in the anesthetized dog. The current experiment investigated the mechanism by which monensin produces relaxation of smooth muscle from the canine coronary artery. Helical strips of coronary artery were mounted in a muscle chamber and made to contract by stimulation with 5 hydroxytryptamine. First, concentration-response curves were established for the relaxant effect of added monensin. Then the following agents were evaluated for their effects on the monensin-induced inhibition of contraction to 5-hydroxytryptamine: aminophylline, indomethacin, propranolol, ouabain, and a potassium-free solution. Finally, the effect of added monensin on potassium-induced relaxation of denervated coronary artery strips was used to further characterize this relaxant effect. The results demonstrate that monensin causes coronary smooth muscle relaxation at the same concentrations reported to cause a positive inotropic effect in isolated myocardial preparations. The monensin-induced inhibition of contraction of the isolated coronary artery was not blocked by aminophyline, propranolol, or indomethacin, demonstrating that the inhibition was not mediated by adenosine, by β-adrenegic receptors, or by prostaglandins. The inhibition of coronary smooth muscle contraction was completely blocked by ouabain or by a potassium-free solution. Monensin also potentiated potassium-induced relaxation of both innervated and denervated coronary artery strips; both the potassium-induced relaxation and the potentiation of this relaxation by monensin were ouabain-blocked. We conclude that monensin produces coronary relaxation by stimulation of Na+,K+-ATPase. This stimulation may result from a monensin-induced increase in intracellular sodium ion concentration similar to the change that, paradoxically, mediates the positive inotropic effect in the myocardium.

Original languageEnglish (US)
Pages (from-to)168-175
Number of pages8
JournalCirculation research
Volume53
Issue number2
DOIs
Publication statusPublished - Jan 1 1983
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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