CHRONIC K-SUPPLEMENTATION DECREASES MYOCARDIAL [NA,K-ATPASE] AND NET K-UPTAKE CAPACITY IN RODENTS

The effects of high K intake on plasma It, myocardial It content and N a,It-ATPase concentration and on myocardial It uptake during KCl infus ion were evaluated in rodents. Myocardial Na,K-ATPase was quantified i n crude homogenates by K-dependent pNPPase activity in rats, and in in tact samples by H-3-ouabain binding in guinea pigs. Na,K-ATPase alpha isoform distribution was assessed by immunoblotting. Plasma It was mon itored in anesthetized rats during intravenous infusion of 0.75 mmol K Cl/100 g body weight/h. A significant increase in plasma K was observe d after 2 days of It supplementation, 4.9+/-0.2 (mean +/- S.E.M.) v 3. 0 +/- 0.2 mmol/l in weight matched controls (P < 0.01, n = 5) and this difference remained stable. After 1 day, a significant myocardial K c ontent increase was obtained, 86.2 +/- 3.0 v 76.7 +/- 1.9 mu mol/g wet weight (P < 0.05, n = 5); after 4 days myocardial K stabilized 4.9 +/ - 1.2 mu mol/g wet weight above control level (P < 0.05, n = 5). From the 4th day, a significant decrease in myocardial K-dependent pNPPase activity was observed, 1.18 +/- 0.04 v 1.31 +/- 0.01 mu mol/min/g wet weight in weight matched controls (P < 0.05, n = 5); after 2 weeks the decrease was 29% (P < 0.05, n = 5), with a reduction in alpha(1)-isof orm abundance by 24% (P < 0.05, n = 5), and a tendency to a decrease i n alpha(2) of 10% (N.S., n = 5). The measurements were validated by H- 3-ouabain binding to myocardial samples from guinea pigs K-supplemente d for 2 weeks, showing a decrease of 21% (P < 0.05, n = 5). During KCl infusion, the myocardial K content increase rate was reduced by 52% ( P < 0.05) in the It-supplemented rats. The observed effects of K-suppl ementation on plasma K, myocardial K content and myocardial K-dependen t pNPPase activity were abolished within 2 days after reallocation to chow with normal K content. In conclusion, high It-intake is associate d with significantly and reversible increased plasma and myocardial It content, and decreased myocardial Na,K-ATPase concentration and net m yocardial It uptake capacity. Thus, the heart is protected from major increases in intracellular K concentrations during chronically-high K- intake. (C) 1998 Academic Press.