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Effects of atorvastatin on systemic and renal NO dependency in patients with non‐diabetic stage II–III chronic kidney disease
Author(s) -
Mose Frank Holden,
Larsen Thomas,
Jensen Janni Majgaard,
Hansen Annebirthe Bo,
Bech Jesper Nørgaard,
Pedersen Erling Bjerregaard
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12390
Subject(s) - atorvastatin , endocrinology , medicine , renal function , kidney disease , angiotensin ii , aquaporin 2 , blood pressure , mechanical engineering , water channel , engineering , inlet
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 ( FE Na ), urinary excretion of aquaporin‐2 (u‐ AQP2 ) and epithelial sodium channels (u‐ ENaC γ ), 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 ‐ ENaC γ , but sodium excretion,C H 2 O, FE Na and u‐ AQP2 were not changed by atorvastatin. L ‐ NMMA reduced renal effect variables, including GFR , FE Na and u‐ ENaC γ 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.