Transient inotropic effects of low extracellular sodium in perfused rat heart.
The inotropic effects of low concentrations of extracellular Na+ (35-110 mM) were studied using Langendorff-perfused rat hearts. Low Na+ induced an initial positive inotropic response proportional to the decrease of transsarcolemmal Na+ gradient. At 35 mM Na+, this effect was followed by a secondary fall in contractility and rise of resting force (RF) and then by a delayed positive inotropic effect and recovery of RF. The magnitude of these low Na(+)-induced transient changes was dependent on the extracellular Ca2+ concentration and was altered by amiloride (6 x 10(-4) and 2.5 x 10(-3) M), ouabain (5 x 10(-5) and 5 x 10(-4) M), ryanodine (2 x 10(-8), 1 x 10(-7) and 1 x 10(-6) M), and sodium azide (1 x 10(-3) and 5 x 10(-3) M) but not by verapamil (2 x 10(-8) and 1 x 10(-7) M) or vanadate (4 x 10(-6) M). The data indicate the initial positive inotropic response of the rat heart to low Na+ may be due to rapid loading of myocytes with Ca2+ through the Na(+)-Ca2+ exchange mechanism. The secondary depression of contractility and the rise of RF appear to be the consequence of the short-lived intracellular Ca2+ overload. Furthermore, the recovery of contractions and the delayed positive inotropic response may be the result of the intracellular redistribution of excessive Ca2+ into the sarcoplasmic reticulum with mitochondria and increased transsarcolemmal Ca2+ efflux apparently playing a more minor role.
Kolar
F
F
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Cole
W C
WC
Ostadal
B
B
Dhalla
N S
NS
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology; D012964:Sodium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019810:Sodium Azide; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D001386:Azides; D012433:Ryanodine; D010042:Ouabain; D000584:Amiloride; D019810:Sodium Azide; D012964:Sodium; D014700:Verapamil; D002118:Calcium