Responses of contractile function to ruthenium red in rat heart.
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.
Gupta
M P
MP
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Innes
I R
IR
Dhalla
N S
NS
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D012430:Ruthenium Red; D000584:Amiloride; D012428:Ruthenium; D012964:Sodium; D014700:Verapamil; D007545:Isoproterenol; D002118:Calcium