Effects of fluvastatin treatment on red blood cell Na+ transport systems in hypercholesterolemic subjects

This study was performed to ascertain the effects of short-term cholesterol -lowering therapy with fluvastatin on red blood cells Na+ transport systems . Forty familial hypercholes terolemic subjects (FH; 19 men and 21 women) w ithout hypertension or cardiovascular disease were given a placebo for 4 we eks, and then randomized in two groups. Twenty (fluvastatin group) were giv en fluvastatin (40 mg/day), and the other 20 (placebo group) continued plac ebo administration. After the placebo period and after 4 and 12 weeks of pl acebo or fluvastatin treatment, we measured Na+/K+ pump activity, Na+/K+ co transport (Na+/K+ Ct), Na+/Li+ countertransport (Na+/Li+ Cnt), passive Napermeability (Na+PP), and internal Na+ content (Na-i(+)). The same paramete rs were measured in 23 control subjects (C) with normal cholesterolemic val ues, who were matched for sex and age. FH had higher Na+/Li+ Cnt values tha n C (193.2 +/- 59.4 vs. 139.8 +/- 48.7 mu M cells/h; p < 0.01), an increase in Na+PP (0.034 +/- 0.012/h vs. 0.018 +/- 0.004/h; p < 0.001), and higher Na-i(+) (7.5 +/- 1.5 vs. 6.2 +/- 0.9 mM cells; p < 0.001). In hypercholeste rolemic subjects, Na-i(+), values were correlated with cholesterol (total a nd LDL) and apo B levels, whereas an inverse correlation was found for HDL- c and apo AI levels. Reduced total and LDL cholesterol and apo B levels aft er fluvastatin treatment caused a decrease in both Na+/Li+ Cnt (from 186.1 +/- 60.5 to 125.1 +/-34.0 mu M cells/h; p < 0.001) and Na+ PP (from 0.035 /- 0.013/h to 0.02 +/- 0.016/h: p < 0.01), and an increase in Na+/K+ pump a ctivity (from 1,549.0 +/- 507.7 to 1,894.2 +/- 536.2 mu M cells/h p < 0.04) , with a significant reduction in the internal Na+ content (from 7.5 +/- 1. 6 to 5.8 +/- 2. 1 mM cells: p < 0.001). Our findings show that hypercholes terolemia affects red blood cell Na+ transport systems, with an increase in Na+/Li(+)Cnt, Na+PP, and the internal Na+ content. Cholesterol-lowering tr eatment with fluvastatin influences Na+ transport systems and reduces the i nternal Na+ content. This might also be responsible for the greater vascula r reactivity observed in hypercholesterolemic patients, and its amelioratio n after a reduction in cholesterol levels.