Attenuation of cyclosporine-induced hypertension by dietary fatty acids in the borderline hypertensive rat.
The effects of dietary (10% calories) safflower (SAF), evening primrose (EPO), and fish oil (F) as sources of linoleic acid (control), gamma-linolenic acid, and long-chain n-3 fatty acids, respectively, on cardiovascular and renal responses to chronic (5 weeks) cyclosporine administration were studied in male borderline hypertensive rats. In one experiment (n = 9/group), oral administration of CsA at 0.1 mg/kg.day significantly increased awake systolic blood pressure vs. placebo in SAF-fed rats (P less than 0.01). This increase was prevented by both EPO (P less than 0.001) and F (P less than 0.01), in the absence of group differences in body weight gain or plasma electrolyte levels. In a second experiment, CsA also increased blood pressure vs. placebo in SAF-fed rats (P less than 0.001). While this increase was prevented by EPO (P less than 0.001), F had no significant effect. Differences in group blood pressure responses were not explained by group differences in body weight gain or trough levels of blood CsA. Renal function, assessed in anesthetized rats after week 5, demonstrated a CsA-related (10 mg/kg.day) decrease in whole-kidney GFR in SAF-fed animals vs. placebo (P less than 0.05) that was prevented by EPO and attenuated by F. EPO and F also tended to reduce the CsA-induced elevation in renovascular resistance, but this difference did not reach statistical significance. These findings suggest the potential of dietary EPO and F to offset nephrotoxic effects of CsA administration, and suggest that EPO may also be useful in countering CsA-induced hypertension.
Mills
D E
DE
Department of Health Studies, University of Waterloo, Ontario, Canada.
Ward
R P
RP
McCutcheon
D
D
Dixon
H
H
Ly
H
H
Scholey
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation
D004042:Dietary Fats, Unsaturated; D016572:Cyclosporine