Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation and oxidative stress. A ‘pleiotropic’ property of statins receiving less attention is their effect on the autonomic nervous system. Increased central sympathetic outflow and diminished cardiac vagal tone are disturbances characteristic of a range of cardiovascular conditions for which statins are now prescribed routinely to reduce cardiovascular events: following myocardial infarction, and in hypertension, chronic kidney disease, heart failure and diabetes. The purpose of the present review is to synthesize contemporary evidence that statins can improve autonomic circulatory regulation. In experimental preparations, high-dose lipophilic statins have been shown to reduce adrenergic outflow by attenuating oxidative stress in central brain regions involved in sympathetic and parasympathetic discharge induction and modulation. In patients with hypertension, chronic kidney disease and heart failure, lipophilic statins, such as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle sympathetic nerve activity) by 12–30%. Reports concerning the effect of statin therapy on HRV (heart rate variability) are less consistent. Because of their implications for BP (blood pressure) control, insulin sensitivity, arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions should be considered additional mechanisms by which statins lower cardiovascular risk.
- blood pressure
- nitric oxide
- oxidative stress
- sympathetic nervous system
Abbreviations: AngII, angiotensin II; AT1 receptor, angiotensin type 1 receptor; BP, blood pressure; DBP, diastolic BP; ET-1, endothelin-1; GABA, γ-aminobutyric acid; HF, high-frequency; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; HR, heart rate; HRV, heart rate variability; icv, intracerebroventricular; LDL, low-density lipoprotein; LF, low-frequency; L-NAME, NG-nitro-L-arginine methyl ester; L-NMMA, NG-monomethyl-L-arginine; LVEF, left ventricular ejection fraction; MAP, mean arterial pressure; MIBG, metaiodobenzylguanidine; MSNA, muscle sympathetic nerve activity; NE, noradrenaline; NOS, nitric oxide synthase; eNOS, endothelial NOS; nNOS, neuronal NOS; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; O2−, superoxide anion; pNN50, percentage of consecutive normal RR intervals that differ by more than 50 ms; RMSSD, square root of the mean square difference of successive RR intervals; ROCK, Rho-associated kinase; ROS, reactive oxygen species; RSNA, renal sympathetic nerve activity; RVLM, rostral ventrolateral medulla; SBP, systolic BP; SDNN, S.D. of consecutive normal R-wave to R-wave intervals; SHRSP, stroke-prone spontaneously hypertensive rat; SOD, superoxide dismutase; Mn-SOD, manganese SOD; TBARS, thiobarbituric acid-reactive substance; WKY rat, Wistar–Kyoto rat
- © The Authors Journal compilation © 2014 Biochemical Society