Fat diet, osmotic fragility of erythrocytes and inotropic response of rat 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 plasma (low density lipoprotein endocytosis). The drug might exert effects 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 muscle. We have therefore studied osmotic fragility of erythrocytes and inotropic and lusitropic responses of isolated heart papillary muscles taken 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 lovastatin, or similar diets in which 4 g/100 g diet of the olive oil was replaced by cod liver oil. Three weeks feeding of a high fat diet containing cod liver oil did not affect osmotic fragility of erythrocytes or indices of inotropy or lusitropy in papillary muscles in response to noradrenaline 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 lovastatin was added to this diet the osmotic fragility was increased for the whole population of erythrocytes. In this situation the "relaxation-onset index"--an index of early relaxation in the papillary muscles--was shifted to higher concentrations of noradrenaline. Thus, intake of lovastatin may lead to an early appearance of effects of dietary fat on osmotic fragility of erythrocytes and on heart muscle responses to catecholamines. These effects of lovastatin are, however, apparently dependent upon the kind of dietary fat as they are prevented by the presence of cod liver oil.
Skomedal
T
T
Department of Pharmacology, University of Oslo, Norway.
Høstmark
A T
AT
Osnes
J B
JB
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D004912:Erythrocytes / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D009996:Osmotic Fragility; D010210:Papillary Muscles / Q000502:physiology; D051381:Rats
D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D008148:Lovastatin; D009638:Norepinephrine