FAT DIET, OSMOTIC FRAGILITY OF ERYTHROCYTES AND INOTROPIC RESPONSE OFRAT-HEART PAPILLARY-MUSCLE TO NORADRENALINE STIMULATION - EARLY APPEARANCE OF THE DIET EFFECT BY LOVASTATIN

Intake of lovastatin, an inhibitor of endogenous cholesterol synthesis , leads to a compensatory increase in the uptake of cholesterol from p lasma (low density lipoprotein endocytosis). The drug might exert effe cts also by facilitating uptake of fatty acids carried in low density lipoprotein. It has been reported that dietary fat may alter physical properties of erythrocytes as well as adrenergic effects in heart musc le. We have therefore studied osmotic fragility of erythrocytes and in otropic and lusitropic responses of isolated heart papillary muscles t aken from rats fed for 3 weeks either a purified high fat diet (olive oil/coconut oil 16 g/6 g/100 g diet), prepared plus and minus lovastat in, or similar diets in which 4 g/100 g diet of the olive oil was repl aced by cod liver oil. Three weeks feeding of a high fat diet containi ng cod liver oil did not affect osmotic fragility of erythrocytes or i ndices of inotropy or lusitropy in papillary muscles in response to no radrenaline stimulation neither in the absence nor in the presence of lovastatin. In contrast, purified high fat diet lacking cod liver oil increased osmotic fragility in a fraction of the erythrocytes. When lo vastatin was added to this diet the osmotic fragility was increased fo r the whole population of erythrocytes. In this situation the ''relaxa tion-onset index'' - an index of early relaxation in the papillary mus cles - was shifted to higher concentrations of noradrenaline. Thus, in take of lovastatin may lead to an early appearance of effects of dieta ry fat on osmotic fragility of erythrocytes and on heart muscle respon ses to catecholamines. These effects of lovastatin are, however, appar ently dependent upon the kind of dietary fat as they are prevented by the presence of cod liver oil.