Effects of atorvastatin on systemic and renal NO dependency in patients with non-diabetic stage II-III chronic kidney disease

Abstract

Aims: Clinical trials suggest that statins have beneficial effects on the cardiovascular system independent from their cholesterol lowering properties. In patients with chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-N(G) -monomethyl arginine (L-NMMA) as an inhibitor of NO production.

Methods: In a randomized, placebo-controlled, crossover study patients were treated with atorvastatin for 5 days with standardized diet and fluid intake. Glomerular filtration reate (GFR), fractional excretions of sodium (FENa ), urinary excretion of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ ), vasoactive hormones (renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide) and central blood pressure (BP) estimated by applanation tonometry were measured before and after systemic administration of the NO inhibitor L-NMMA.

Results: Atorvastatin caused a significant reduction in U-ENaCγ , but sodium excretion, C H 2 O , FENa and u-AQP2 were not changed by atorvastatin. L-NMMA reduced renal effect variables, including GFR, FENa and u-ENaCγ and increased brachial BP and central BP to a similar extent during both treatments. Vasoactive hormones were changed in the same way by L-NMMA during atorvastatin and placebo treatment.

Conclusion: During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, the data do not support that atorvastatin changes nitric oxide availability in patients with mild nephropathy. The reduced u-ENaC may reflect changes in sodium absorption in the nephron induced by atorvastatin.

Keywords: atorvastatin; chronic kidney disease; epithelial sodium channels; fractional excretion of sodium; nitric oxide.

Figure 1

Mean arterial pressure (MAP) in a randomized, placebo-controlled, crossover study of patients with chronic kidney disease stage II and III during atorvastatin and placebo treatment. The effect of L-NMMA infusion was measured. Baseline BP was defined as a mean of the measurements 30 min prior to L-NMMA infusion. Baseline MAP was similar in both treatments groups (P = NS). Stable BP was achieved for the last 45 min of L-NMMA infusion. A mean of the measurements from last 45 min of L-NMMA infusion was used to calculate changes from baseline. Values represent mean ± SEM, n = 25. , placebo; , atorvastatin