Interaction of dietary fatty acids and cyclosporine A in the borderline hypertensive rat: tissue fatty acids.
In this study we examined (i) the effects of cyclosporine A (CS) on tissue lipid composition and (ii) the effect of changes in dietary n-6 fatty acids on tissue responses to CS. Fatty acid composition of liver, kidney, heart and brain were determined after 4 wk of treatment with CS (10 mg/kg.d p.o.) in male borderline hypertensive rats (BHR, n = 4/group), whose diet was supplemented with either safflower oil or evening primrose oil (EPO). Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine/phosphatidylinositol, triglyceride and cholesteryl ester fatty acids were measured in kidney, heart, brain and liver. The same parameters were also measured in safflower-fed BHR (n = 4) receiving placebo. The effects of CS on liver microsomal delta 9, delta 6 and delta 5 desaturases in vitro were also followed. CS affected the fatty acid composition of all tissues examined, with the greatest changes seen in the renal phosphatidylcholine and phosphatidylserine/phosphatidylinositol fractions. All CS-induced changes that occurred in the liver, brain and renal fatty acids were reversed by EPO. CS elevated delta 9 desaturase but had no effect on delta 6 and delta 5 desaturase. In light of (i) the observation that EPO normalizes renal function and blood pressure in CS-treated BHR, and (ii) the importance of the kidney in blood pressure regulation, the data suggest that the beneficial effects of EPO on CS toxicity may involve changes in renal phospholipid fatty acid profiles.
Mills
D E
DE
Department of Health Studies, University of Waterloo, Ontario, Canada.
de Antueno
R
R
Scholey
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000302:isolation & purification / Q000378:metabolism*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D010938:Plant Oils; D016572:Cyclosporine; D044943:Fatty Acid Desaturases