title: Simvastatin reduces sympathetic outflow and augments endothelium-independent dilation in non-hyperlipidaemic primary hypertension.
abstract: OBJECTIVE
  Previous reports, involving hypercholesterolaemic hypertensive subjects, that statins reduce muscle sympathetic nerve activity (MSNA) did not investigate potential neural sites of such sympathoinhibition or determine its consequences for endothelial function or insulin resistance. This study of hypertensive subjects with lower plasma cholesterol tested the hypotheses that lipophilic simvastatin would attenuate resting sympathoexcitation and augment baroreflex modulation of MSNA and heart rate (HR), flow-mediated vasodilation and insulin sensitivity.
  
  
  METHODS
  Prospective, randomised, double-blind, placebo-controlled crossover study.
  
  
  METHODS
  Academic hospital-based study.
  
  
  METHODS
  Fourteen non-hyperlipidaemic primary hypertensive subjects (10 men; overall mean±SD age 58±12 years).
  
  
  METHODS
  Four weeks of simvastatin (80 mg/day) or placebo.
  
  
  METHODS
  Resting blood pressure (BP), HR, MSNA, spontaneous arterial baroreflex MSNA and HR modulation, endothelium-dependent and endothelium-independent vasodilation, and the homoeostatic model assessment of insulin resistance (HOMA-IR).
  
  
  RESULTS
  Simvastatin lowered MSNA burst frequency (from 32±12 to 25±9 bursts/min) and MSNA burst incidence (from 55±23% to 43±17%; all p<0.01) without affecting BP, HR, baroreflex modulation of either MSNA or HR, or HR variability (all p>0.05). Plasma glucose, insulin, HOMA-IR and endothelium-dependent vasodilation (all p>0.05) were unchanged, whereas endothelium-independent vasodilation increased (7.1±3.8% to 9.7±3.9%, n=13; p<0.01). The fall in MSNA was unrelated to the decrease in low-density lipoprotein cholesterol (r=0.41, p=0.14).
  
  
  CONCLUSIONS
  These findings are consistent with the concept that, in non-hyperlipidaemic subjects with primary hypertension, simvastatin causes a cholesterol-independent reduction in an elevated central set-point for MSNA, without affecting arterial baroreflex modulation of either MSNA or HR. There may be less neurogenic constraint on endothelium-independent vasodilation as a consequence.
authors.affiliation: University Health Network and Mount Sinai Hospital Division of Cardiology, University of Toronto, 600 University Avenue, Toronto, Ontario, Canada.
authors.forename: Cheri L
authors.initials: CL
authors.lastname: McGowan
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Murai
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Millar
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Notarius
authors.forename: Beverley L
authors.initials: BL
authors.lastname: Morris
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D001158:Arteries / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin