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Responses of contractile function to ruthenium red in rat heart.

Abstract
Isolated rat hearts exhibited a biphasic contractile response to varying concentrations of ruthenium red. A negative inotropic effect was observed with concentrations of 0.025-0.5 microM, whereas a reversal of these initial changes toward control or even exceeding the predrug values was obtained as ruthenium red concentration was increased to 2.5 or 5.0 microM. High concentrations (12.5-25.0 microM) of ruthenium red caused a sustained contracture. In contrast, isolated frog hearts exhibited only a sustained negative inotropic effect at 0.25-12.5 microM ruthenium red. In studies with rat heart, both negative and positive inotropic effects of 2.5 microM ruthenium red were blocked either by increasing the concentration of Ca2+ (from 1.25 to 5.0 mM) or by decreasing the concentration of Na+ (from 140 to 35 mM) in the perfusion medium. The contracture induced by 12.5 microM ruthenium red was markedly inhibited when Ca2+ in the medium was lowered. The positive inotropic effect and contracture due to ruthenium red were also blocked by 1 microM of verapamil and 1.5 mM of amiloride; however, these interventions did not prevent the initial negative inotropic effect of ruthenium red. These experiments suggest the role of extracellular Ca2+ in the dose- and time-dependent effects of ruthenium red on contractile function of the rat heart. Furthermore, the positive inotropic response to ruthenium red may be related to its actions on the Na+-dependent Ca2+ movements in the cardiac cell.
AuthorsM P Gupta, I R Innes, N S Dhalla
JournalThe American journal of physiology (Am J Physiol) Vol. 255 Issue 6 Pt 2 Pg. H1413-20 (Dec 1988) ISSN: 0002-9513 [Print] UNITED STATES
PMID2462366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Ruthenium Red
  • Amiloride
  • Ruthenium
  • Sodium
  • Verapamil
  • Isoproterenol
  • Calcium
Topics
  • Amiloride (pharmacology)
  • Animals
  • Calcium (pharmacology)
  • In Vitro Techniques
  • Isoproterenol (pharmacology)
  • Male
  • Myocardial Contraction (drug effects)
  • Perfusion
  • Rats
  • Rats, Inbred Strains
  • Reference Values
  • Ruthenium (pharmacology)
  • Ruthenium Red (pharmacology)
  • Sodium (pharmacology)
  • Verapamil (pharmacology)

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