Autosomal dominant polycystic kidney disease (ADPKD) is the most common life threatening hereditary disease and is the fourth most common cause of end stage kidney disease. Preclinical studies to identify effective interventions to prevent or slow progression of PKD nephropathy are therefore direly needed. Heterozygous Han:SPRD rats are an autosomal dominant PKD model with many of the characteristics of ADPKD in humans. In the present study, parameters known to antedate the decrease in renal function, namely renal structure, renal blood flow (RBF) and mean arterial pressure (MAP), were evaluated with three different interventions, namely HMG-CoA reductase inhibition with lovastatin, angiotensin converting enzyme (ACE) inhibition with enalapril, and a combination of these two treatments. The statin therapy demonstrated structural and functional benefits, including increased RBF and decreased BUN, independent of a change in MAP, while the ACE inhibition therapy demonstrated structural benefit in association with a decrease in MAP. An enhancement of these protective interventions in this autosomal dominant PKD model was not demonstrated with the combined treatment.