Sympathoinhibition by atorvastatin in hypertensive patients

Circ J. 2010 Nov;74(12):2622-6. doi: 10.1253/circj.cj-10-0427. Epub 2010 Oct 9.

Abstract

Background: Experimental animal data suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) might reduce enhanced sympathetic activity, a hallmark of hypertensive patients. This hypothesis was tested for the first time in patients with primary hypertension.

Methods and results: Using a prospective, randomized, placebo-controlled, double-blind, cross-over design, a proof-of-principle trial was performed in 13 patients with mild to moderate primary hypertension, who were randomly assigned to a regimen of atorvastatin (80mg/day) for 3 weeks, followed by placebo for 3 weeks or to a regimen of placebo for 3 weeks, followed by atorvastatin (80mg/day) for 3 weeks. Microneurography was used at the end of each treatment period to measure sympathetic nervous system activity (muscle sympathetic nerve activity: MSNA). Heart rate variability (HRV) and plasma norepinephrine concentrations were also measured. Additionally, effects on blood pressure (BP) and heart rate (HR) were assessed by 24-h ambulatory BP measurement. Atorvastatin reduced postganglionic MSNA (atorvastatin 35.0±2.0 vs placebo: 39.2±1.5 bursts/min, P=0.008) and heart frequency corrected MSNA (atorvastatin: 58.5±2.0 vs placebo: 64.7±3.0 bursts/100 beats, P=0.02). Atorvastatin had no significant effect on plasma norepinephrine levels, HRV, BP or HR.

Conclusions: In patients with mild to moderate hypertension, atorvastatin reduces postganglionic MSNA, which supports the hypothesis that HMG-CoA reductase plays a role in sympathetic nervous system activity.

Trial registration: ClinicalTrials.gov NCT00497016.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Atorvastatin
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypertension / blood*
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Prospective Studies
  • Pyrroles / pharmacology*
  • Sympathetic Nervous System / physiopathology*
  • Time Factors

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin
  • Norepinephrine

Associated data

  • ClinicalTrials.gov/NCT00497016