Anti-sympathetic action enhances statin's pleiotropic effects: the combined effect of rosuvastatin and atenolol on endothelial function

Int Angiol. 2014 Feb;33(1):27-34.


Aim: Assessment of flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery by a new device (UNEXEF18G) has been reported to be excellent for evaluating endothelial function, and sympathetic overdrive can accelerate the atherosclerotic process. The purpose of this study was to investigate and confirm whether anti-sympathetic beta-blocking action can enhance the pleiotropic effects of statins.

Methods: FMD and NMD were measured using the UNEXEF18G before and after 4-week treatment of rosuvastatin (5 mg/day) with or without atenolol (25 mg/day) in 44 hypercholesterolemic patients (70±8 years old, LDL-C >140 mg/dL) with hypertension. Patients were randomly allocated to two treatment arms: rosuvastatin alone (R-group, N.=22) and rosuvastatin with atenolol (RA-group, N.=22).

Results: Baseline FMD was not different between the two treatment arms, and both groups showed improvement in FMD (R-group, 3.48±1.9% to 4.65±2.41%, P<0.05; RA-group, 3.42±1.48% to 5.46±1.79%, P<0.05), while there were no differences in NMD. The effects on lipid profiles were identical in the two groups. In addition, FMD improvement was greater in the RA-group than in the R-group (Δchange 2.15±1.29% vs. 1.16±1.15%, P<0.05).

Conclusion: Beta-blockade enhances the pleiotropic effects of statins on endothelial function. The mechanism should be confirmed by further studies.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / therapeutic use*
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Atenolol / therapeutic use*
  • Biomarkers / blood
  • Brachial Artery / drug effects*
  • Brachial Artery / physiopathology
  • Cholesterol, LDL / blood
  • Drug Interactions
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Fluorobenzenes / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Japan
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vasodilator Agents / therapeutic use*


  • Adrenergic beta-1 Receptor Antagonists
  • Antihypertensive Agents
  • Biomarkers
  • Cholesterol, LDL
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • Vasodilator Agents
  • Atenolol
  • Rosuvastatin Calcium