Dietary alteration of dihomogamma-linolenic acid/arachidonic acid ratio in a rat 5/6-renal-ablation model. The Nutrition & Kidney Disease Research Group.

Interest in the modulation of renal diseases by polyunsaturated fatty acids (PUFA) led this group to examine the effects of borage oil (BO) and corn oil (CO) in the rat 5/6-renal-ablation model. BO is a rich source of gamma-linolenic acid (GLA; 18:3n-6), which is elongated to dihomogamma-linolenic acid (DGLA; 20:3n-6). CO is a rich source of linoleic acid (LA; 18:2n-6), a GLA and arachidonic acid (AA; 20:4n-6) precursor. The purpose of this study was to assess whether an increased DGLA:AA ratio as provided by BO would confer benefits beyond those provided by LA present in corn oil. Forty rats were used for the experiment. Seven rats were used for presurgery measurements. The remaining animals were subjected to 5/6 nephrectomy. Surviving rats (N = 30) were fed regular laboratory diet (RLD) for 7 days, at which time seven rats were used to obtain 1-wk postnephrectomy data. The remainder were then allocated to receive either RLD (N = 8), 15% BO (N = 8), or 15% CO (N = 7) diets for 20 wk. Body weight, renal phospholipid levels, renal function (proteinuria and GFR), glomerular histology, glomerular macrophage infiltration, urinary prostaglandin levels (thromboxane B2 (TxB2), 6-keto-PGF1 alpha), plasma lipid levels, and blood pressure were measured. Diets were well tolerated by all groups with a similar age-related gain in weight throughout the study. Efficacy of the PUFA diets was confirmed by alteration in renal tissue phospholipids; LA decreased in the RLD and BO groups, but not in the CO group. AA was higher in the BO and CO rats, but only the BO group showed a rise in GLA and DGLA incorporation. Proteinuria increased progressively in the RLD group but remained at 1-wk postsurgery levels in the BO and CO groups. Decline in GFR and mesangial expansion were significantly lessened by BO supplementation only. Both PUFA diets limited glomerulosclerosis and macrophage infiltration, but direct comparisons between BO and CO groups revealed significantly less glomerulosclerosis and macrophage infiltration in the BO group. Both BO and CO attenuated the rise in the TxB2 excretion rate and restored the 6-keto-PGF1 alpha:TxB2 ratio to the 1-wk postsurgery level. Plasma lipid levels rose in all groups, but the rise in cholesterol level was less in the BO and CO rats, CO being the most efficacious in this regard. BP increased progressively in RLD rats, but not in the BO and CO groups, BO providing a markedly greater hypotensive effect. In summary, both CO and BO supplemented PUFA diets limited glomerular injury in the renal-ablated rats. However, BO supplementation was more effective than CO supplementation at preserving GFR, limiting mesangial expansion and glomerulosclerosis, and reducing glomerular macrophage infiltration.

Dietary supplementation with L-arginine limits cell proliferation in the remnant glomerulus.

One effect of L-arginine is to increase nitric oxide (NO) production by endothelial cells. NO directly reduces endothelin-1 production by endothelial cells and also inhibits platelet-derived growth factor (PDGF) induced cell proliferation. Since subtotal renal ablation is associated with an early phase of cell proliferation in the glomerulus that precedes injury, we examined the effect of dietary supplementation with L-arginine on glomerular cell proliferation and expression of the cytokine endothelin-1 (ET-1). A first group of renal-ablated rats was untreated. A second group of renal-ablated rats received L-arginine (1%) in the drinking water. Two weeks after subtotal ablation renal cortical tissue was snap frozen for immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) expression and ET-1. Protein and total RNA was extracted from sieved glomeruli. mRNA levels were quantitated by co-amplification RT-PCR utilizing specific 5' and 3' primers for rat ET-1 and beta-actin. L-arginine reduced the number of PCNA positive nuclei in remnant glomeruli, and Western blot Analysis of glomerular proteins also showed that L-arginine reduced PCNA expression. Glomerular ET-1 mRNA levels and protein immunostaining declined in the rats receiving L-arginine. We conclude that dietary supplementation with L-arginine reduces early cell proliferation in the remnant glomerulus, an effect that may be mediated, in part, by a decrease in ET-1 production.

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 +/- 9off/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).(ABSTRACT TRUNCATED AT 250 WORDS)