Atorvastatin improves sodium handling and decreases blood pressure in salt-loaded rats with chronic renal insufficiency

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 28; no. 9; pp. e23 - e28
• Main Authors: Juncos, Luis I., M.D., Ph.D, Martín, Fernando L., M.D, Baigorria, Sandra T., Lab.Tech, Pasqualini, María E., Ph.D, Fiore, María C., Ph.D, Eynard, Aldo R., M.D., Ph.D, Juncos, Luis A., M.D, García, Néstor H., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2012; Elsevier Limited
• Subjects: Animals; Atorvastatin Calcium; Blood pressure; Blood Pressure - drug effects; Body weight; Cardiovascular disease; Creatinine - blood; Diet; Fatty Acids, Unsaturated - urine; Gastroenterology and Hepatology; Health risks; Heart Ventricles - drug effects; Heptanoic Acids - pharmacology; Heptanoic Acids - therapeutic use; Hydroxymethyl glutaryl coenzyme A reductase inhibition; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Hypertension - metabolism; Kidney - drug effects; Kidney - metabolism; Kidney diseases; Male; Nephrectomy; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric oxide/oxidant stress; Nitrites; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Proteins; Proteinuria - drug therapy; Proteinuria - etiology; Pyrroles - pharmacology; Pyrroles - therapeutic use; Random Allocation; Rats; Rats, Sprague-Dawley; Renal failure; Renal function; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - metabolism; Retention; Rodents; Salt sensitivity; Salts; Sodium; Sodium - adverse effects; Sodium - metabolism; Sodium balance; Sodium Chloride, Dietary - adverse effects; Sodium Chloride, Dietary - metabolism; Hydroxymethyl glutaryl coenzyme A reductase inhibition; Sodium balance; Salt sensitivity; Nitric oxide/oxidant stress; Renal failure
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2012.02.008

Abstract Objective Oxidative stress and inflammation seem to mediate the cardiovascular risks associated with salt sensitivity. Because hydroxymethyl glutaryl coenzyme A reductase inhibitors decrease oxidation and increase nitric oxide (NO) synthesis, we examined the effects of atorvastatin (ator) on tissue injury in rats with a reduced renal mass produced by 5/6 nephrectomy. This salt-sensitive hypertension model causes kidney and cardiovascular injuries. Methods After undergoing 5/6 nephrectomy or sham surgery, male Sprague–Dawley rats were randomized into five groups: sham, reduced renal mass and a normal salt diet (NNaD), NNaD+ator (50 mg · kg−1 · d−1 ), reduced renal mass and a high salt diet (HNaD), and HNaD+ator. After assessing the sodium balance for 7 d, we measured blood pressure (BP), creatinemia, proteinuria, nitrites, and 12(S)-hydroxy 5,8,10-heptadecatrienoic acid, the renal cortical expression of endothelial NO synthase, and the ratio of left ventricular weight to body weight. Results In NNaD rats, creatinine, proteinuria, and 12(S)-hydroxy 5,8,10-heptadecatrienoic acid increased, renal NO indices decreased, but the Na+ balance, BP, and the left ventricular weight/body weight ratio remained unchanged. In the NNaD group, atorvastatin normalized the NO indices and decreased BP and proteinuria, although the remaining parameters continued unchanged. In contrast, HNaD increased creatinemia, proteinuria, and 12(S)-hydroxy 5,8,10-heptadecatrienoic acid excretion rates and decreased renal endothelial NO synthase. Salt retention was accompanied by increased BP and ventricular weight. In this HNaD group, atorvastatin prevented a BP increase, partly decreased sodium retention, but failed to improve NO indices, proteinuria, oxidant stress, and the left ventricular weight/body weight ratio. Conclusion Atorvastatin exerts beneficial effects on renal function, injury, and salt sensitivity in rats with a reduced renal mass on an NNaD. The HNaD hampers these beneficial effects.