DIETARY FATTY-ACIDS AND THE GLOMERULAR HEMODYNAMIC-RESPONSE TO CYCLOSPORINE IN BORDERLINE HYPERTENSIVE RATS

We have recently reported that cyclosporine A (CsA) decreases glomerular filtration rate in the borderline hypertensive rat (BHR), but that the glomerular filtration rate is normal when the rats are maintained on a diet supplemented with evening primrose (EP) oil. The current studies were designed to determine the glomerular hemodynamic changes responsible for this effect. A first group (PLAC-SAFF) received a diet supplemented with safflower oil (SAFF) (10% of calories) and placebo (PLAC). A second group (CsA-SAFF) received a diet supplemented with SAFF and CsA (10 mg/kg/day). A third group (CsA-EP) also received CsA, but the diet was supplemented with EP oil (10% of calories). Routine micropuncture studies were performed after five to nine weeks of treatment. Single nephron glomerular filtration rate (SNGFR) was lower in CsA-SAFF than in PLAC-SAFF (36 +/- 2 vs. 46 +/- 1 nl/min, p < 0.05). Maintenance of SNGFR in CsA-EP compared to CsA-SAFF (48 +/- 2 nl/min vs. 36 +/- 2 nl/min, P < 0.05) was due to higher values for single nephron plasma flow rate (156 +/- 16 vs. 118 +/- 9 nl/min, P < 0.05), and higher values for the glomerular capillary ultrafiltration coefficient (0.091 +/- 0.013 vs. 0.054 +/- 0.010 nl/s/mm Hg, P < 0.05). Since dietary fatty acids can affect prostaglandin (PG) production, we measured PGE production in isolated glomeruli. Mean values for basal production rates of PGE were greater in rats maintained on EP than in rats maintained on SAFF (3958 +/- 105 vs. 3378 +/- 146 pg PGE/mg glomerular protein, P < 0.05). Increased renal vasodilatory PG production may be responsible, at least in part, for the maintenance of normal SNGFR in CsA-EP rats.