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


CONCLUSIONS
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.
Fundación J. Robert Cade, CONICET, Córdoba, Argentina.
Luis I
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Fernando L
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Martín
Sandra T
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Baigorria
María E
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Pasqualini
María C
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Fiore
Aldo R
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Eynard
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Néstor H
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García
D000818:Animals; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D004032:Diet; D005231:Fatty Acids, Unsaturated / Q000652:urine; D006352:Heart Ventricles / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009392:Nephrectomy; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D012964:Sodium / Q000009:adverse effects* / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; C023007:12-hydroperoxy-5,8,10-heptadecatrienoic acid; D012964:Sodium; D000069059:Atorvastatin; D003404:Creatinine; D019001:Nitric Oxide Synthase