Sympathoinhibition by atorvastatin in hypertensive patients.
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.


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.
Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Marc E
ME
Gomes
Cees J
CJ
Tack
Freek W
FW
Verheugt
Paul
P
Smits
Jacques W M
JW
Lenders
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D009638:Norepinephrine