RENAL MICROCIRCULATORY EFFECTS OF LOVASTATIN IN A RAT MODEL OF REDUCED RENAL MASS

Objectives, Patients with reduced renal mass are at increased risk of developing renal failure. A remnant kidney model has been used to stud y the hemodynamic and structural changes that occur, We recently repor ted that the lipid-lowering agent lovastatin preserves renal function in this model. The purpose of the present study was to determine the s pecific effects of lovastatin on the renal microcirculation of rats wi th reduced renal mass. Methods. We used the rat hydronephrotic kidney preparation with a 5/6 partial nephrectomy. This model allows direct v isualization of preglomerular and postglomerular vessels using videomi croscopy, The diameters and vascular responses to acetylcholine and an giotensin II of the interlobular, afferent, and efferent vessels were determined in two groups of animals with renal mass reduction: 15 rats with no lovastatin treatment and 18 rats treated with oral lovastatin (15 mg/kg body weight/day) for 2 weeks. Results. In the lovastatin-tr eated rats, the baseline efferent vessel diameter was smaller by 21% ( P < 0.05), but the interlobular and afferent vessel baseline diameters were not different from those in the untreated rats. Serum creatinine levels were lower in the treated rats (1.5 +/- 0.1 versus 2.0 +/- 0.2 mg/dL, P < 0.05), but serum lipids were not different. In the lovasta tin-treated rats, vascular reactivity to acetylcholine was enhanced in the afferent and decreased in the efferent vessels. Conclusions. In t his renal ablation model, lovastatin preserved renal function as measu red by serum creatinine without lowering plasma lipid levels. Lovastat in treatment resulted in smaller efferent vessel diameters. Lovastatin also increased the vasodilatory response to acetylcholine in the affe rent vessels, Together, these preglomerular and postglomerular changes would increase the single-nephron glomerular filtration rate. The ren al protective effect of lovastatin may be due to these vasoactive effe cts on the renal microcirculation. (C) 1997, Elsevier Science Inc. All rights reserved.