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 study the hemodynamic and structural changes that occur. We recently reported that the lipid-lowering agent lovastatin preserves renal function in this model. The purpose of the present study was to determine the specific effects of lovastation on the renal microcirculation of rats with reduced renal mass.

METHODS

We used the rat hydronephrotic kidney preparation with a 5/6 partial nephrectomy. This model allows direct visualization of preglomerular and postglomerular vessels using videomicroscopy. The diameters and vascular responses to acetylcholine and angiotensin 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-treated 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 lovastatin-treated rats, vascular reactivity to acetylcholine was enhanced in the afferent and decreased in the efferent vessels.

CONCLUSIONS

In this renal ablation model, lovastatin preserved renal function as measured by serum creatinine without lowering plasma lipid levels. Lovastatin treatment resulted in smaller efferent vessel diameters. Lovastatin also increased the vasodilatory response to acetylcholine in the afferent vessels. Together, these preglomerular and postglomerular changes would increase the single-nephron glomerular filtration rate. The renal protective effect of lovastatin may be due to these vasoactive effects on the renal microcirculation.