Abstract

Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, is used therapeutically to lower plasma cholesterol levels. However, the effect of this therapy on cell membrane cholesterol in vivo is not known. The goal of this study was to investigate whether lovastatin treatment of hamsters decreases cholesterol in cardiac cell membranes and in red blood cell (RBC) membranes. Because abnormal cellular Ca++ regulation has been associated with altered membrane cholesterol in hearts of cardiomyopathic (CM) hamsters, we also measured the cholesterol content of cardiac and RBC membranes from lovastatin-treated and untreated Bio 14.6 CM hamsters to determine whether any differences existed with respect to normals. Sarcolemma-enriched cardiac membranes and RBC membranes were obtained from 42 to 45-day normal and CM hamsters after 13 days of lovastatin treatment (0.1% of food/day) and from untreated normal and CM hamsters. Plasma cholesterol, membrane cholesterol/phospholipid (C/PL) ratio and cholesterol per milligram of membrane protein (C/prot) were determined. In hearts from untreated CM hamsters, C/prot was significantly lower (P < .05) than in untreated normals. Lovastatin decreased plasma cholesterol by 76% and 81% in normal and CM hamsters, respectively (P < .001), but after lovastatin treatment, there was no significant change in C/PL or C/prot in cardiac membranes from either strain; there was also no significant decrease in C/prot or in C/PL of RBC membranes from normals or C/PL of CM hamster RBC membranes. However, lovastatin feeding resulted in a significant (P < .01) 24% decrease in C/prot of CM RBC membranes.(ABSTRACT TRUNCATED AT 250 WORDS)