To clarify the emerging role of omega-3 fatty acids (FAs) in the regulation of the renal microcirculation, we recently performed micropuncture studies in normal rats maintained on diets enriched with omega-3 FAs. Although those studies suggested that omega-3 FAs alter the renal microcirculation in normal rats, it was not apparent whether this dietary maneuver could modulate intrarenal hemodynamics in the setting of renal disease. Therefore, the present renal micropuncture studies were performed in nephrectomized rats maintained on control diets or diets enriched with omega-3 FAs. Omega-3 FAs abrogated glomerular capillary (56.2 +/- 0.8 vs. 63.9 +/- 2.0 mm Hg) and transcapillary hydraulic pressure (40.9 +/- 1.4 vs. 50.6 +/- 1.3 mm Hg) compared to untreated rats. This effect was attributable to (1) a reduction in mean arterial pressure (138 +/- 3 vs. 163 +/- 2 mm Hg) and (2) a decrease in efferent arteriolar resistance (0.43 +/- 0.06 vs 0.98 +/- 0.19 dyn x seconds x cm-5 x 10(10)). Sclerosis index and albuminuria were also lessened by this dietary maneuver. To further characterize the mechanism of altered renal arteriolar resistance, we then explored the effects of omega-3 FAs on renal prostaglandin synthesis and angiotensin II-stimulated phospholipid turnover. A significant decrease in the urinary excretion of the renal vasoconstrictor, TXA2 (12.8 +/- 2.3 vs. 35.1 +/- 14.0 ng/24 hr), was induced by treatment with omega-3 FAs. Moreover, angiotensin II-stimulated phospholipid turnover was attenuated in intact glomeruli pretreated with omega-3 FAs. We conclude that omega-3 FAs exert favorable effects on experimental renal injury by eliciting a salutary effect on the renal microcirculation of rats subjected to subtotal renal ablation. Moreover, the similarities between these findings and those obtained with sustained inhibition of angiotensin II converting-enzyme suggest that these compounds act through parallel pathways of inhibition.