Prolonged responsiveness to ouabain in hypertrophied rat heart: physiological and biochemical evidence.
The inotropic effect of ouabain on cardiac hypertrophy was evaluated on an isolated Langendorff rat heart preparation with performances registrated by means of an intraventricular balloon. These effects were compared with the drug action on the sarcolemma-bound Na+-K+-ATPase activity. On both normal and pressure-overload induced hypertrophied rat hearts (ventricular wt-to-body wt ratios of 2.1 and 3.3, respectively) the inotropic effect of ouabain (10(-9)-10(-4) M) was evaluated at 0.25 mM external Ca2+. Compared with normal hearts, the recovery of a normal contractile function after the inotropic response was significantly slower in hypertrophied hearts. This was valid with the two protocols applied. During a 30-min washout period, the inotropic response remained nearly unchanged in hypertrophied hearts, whereas it was almost completely reversed in control groups. Sarcolemmal vesicles from both heart groups exhibited high Na+-K+-ATPase activities (sp. act.: 105 +/- 16 mumol X h-1 X mg-1). In both normal and hypertrophied cardiac sarcolemmal preparations, the Na+-K+-ATPase was heterogeneous, with high- and low-sensitivity forms. Their relative proportion was two-to-one. In both heart groups, their respective apparent affinities for ouabain were similar (inhibitory concentration of 50% = 10(-8) and 10(-6) M, respectively). The release of ouabain from these two sites was measured, in washout experiments, by the rates of enzyme relief from inhibition. High- and low-sensitivity forms in hypertrophied heart preparations released ouabain at seven- and threefold lower rates, respectively, than the corresponding forms present in normal cardiac sarcolemmal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000201:enzymology; D004334:Drug Administration Schedule; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D009994:Osmolar Concentration; D010042:Ouabain / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase