TY - JOUR
T1 - Rosuvastatin improves basal nitric oxide activity of the renal vasculature in patients with hypercholesterolemia
AU - Ott, Christian
AU - Schlaich, Markus P.
AU - Schmidt, Bernhard M.W.
AU - Titze, Stephanie I.
AU - Schäufele, Tim
AU - Schmieder, Roland E.
PY - 2008/2
Y1 - 2008/2
N2 - Objective: Impaired endothelium-dependent vasodilation represents an early manifestation of atherosclerosis. Prospective studies have demonstrated that impaired endothelial function in the peripheral circulation of hypercholesterolemic patients predicts CV events and can be restored by statin treatment. Whether this also holds true in the renal circulation has not yet been adequately addressed. Methods: In a double-blind, randomized, placebo-controlled cross-over trial, 40 hypercholesterolemic patients were randomly assigned to receive rosuvastatin (10 mg/day) and matching placebo. The primary objective of the study was to assess the effect of 6-week treatment with rosuvastatin on basal NOS activity of the renal vasculature, as assessed by measuring renal plasma flow (RPF) both before and after blockade of NOS with systemic infusion of NG-monomethyl-l-arginine (l-NMMA). In a subgroup of 20 patients we also studied the effects of a 3-day treatment regimen. Results: Compared to placebo treatment, rosuvastatin decreased LDL-cholesterol levels both after 3 days and 6 weeks of treatment. The decrease in RPF in response to l-NMMA was significantly more pronounced after 6-week therapy with rosuvastatin compared to placebo (-13.7 ± 1.0% versus -11.3 ± 0.7%; p = 0.046), indicating increased basal NOS activity with rosuvastatin treatment. A trend towards improved basal NOS activity was already evident after 3-day treatment. Conclusion: Treatment with rosuvastatin improved basal NOS activity in the renal circulation of hypercholesterolemic patients, suggestive of a nephroprotective effect. In view of the close relation between altered renal function and cardiovascular events, these nephroprotective effects may contribute to the improved CV prognosis associated with statin treatment.
AB - Objective: Impaired endothelium-dependent vasodilation represents an early manifestation of atherosclerosis. Prospective studies have demonstrated that impaired endothelial function in the peripheral circulation of hypercholesterolemic patients predicts CV events and can be restored by statin treatment. Whether this also holds true in the renal circulation has not yet been adequately addressed. Methods: In a double-blind, randomized, placebo-controlled cross-over trial, 40 hypercholesterolemic patients were randomly assigned to receive rosuvastatin (10 mg/day) and matching placebo. The primary objective of the study was to assess the effect of 6-week treatment with rosuvastatin on basal NOS activity of the renal vasculature, as assessed by measuring renal plasma flow (RPF) both before and after blockade of NOS with systemic infusion of NG-monomethyl-l-arginine (l-NMMA). In a subgroup of 20 patients we also studied the effects of a 3-day treatment regimen. Results: Compared to placebo treatment, rosuvastatin decreased LDL-cholesterol levels both after 3 days and 6 weeks of treatment. The decrease in RPF in response to l-NMMA was significantly more pronounced after 6-week therapy with rosuvastatin compared to placebo (-13.7 ± 1.0% versus -11.3 ± 0.7%; p = 0.046), indicating increased basal NOS activity with rosuvastatin treatment. A trend towards improved basal NOS activity was already evident after 3-day treatment. Conclusion: Treatment with rosuvastatin improved basal NOS activity in the renal circulation of hypercholesterolemic patients, suggestive of a nephroprotective effect. In view of the close relation between altered renal function and cardiovascular events, these nephroprotective effects may contribute to the improved CV prognosis associated with statin treatment.
KW - Endothelium
KW - Hypercholesterolemia
KW - l-NMMA
KW - Nitric oxide (NO)
KW - Rosuvastatin
UR - http://www.scopus.com/inward/record.url?scp=38349120435&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2006.12.020
DO - 10.1016/j.atherosclerosis.2006.12.020
M3 - Article
C2 - 17298834
AN - SCOPUS:38349120435
VL - 196
SP - 704
EP - 711
JO - Journal of Atherosclerosis
JF - Journal of Atherosclerosis
SN - 0021-9150
IS - 2
ER -