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Simvastatin reduces sympathetic outflow and augments endothelium-independent dilation in non-hyperlipidaemic primary hypertension . OBJECTIVES 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 . DESIGN Prospective , randomised , double-blind , placebo-controlled crossover study . SETTING Academic hospital-based study . PATIENTS Fourteen non-hyperlipidaemic primary hypertensive subjects ( 10 men ; overall mean±SD age 58±12 years ) . INTERVENTIONS Four weeks of simvastatin ( 80 mg/day ) or placebo . MAIN OUTCOME MEASURES 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 .
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Intervention_Pharmacological
Simvastatin
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Intervention_Pharmacological
simvastatin
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Outcome_Physical
Resting blood pressure ( BP )
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Outcome_Physical
low-density lipoprotein cholesterol
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Participant_Condition
non-hyperlipidaemic primary hypertension
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Participant_Condition
hypercholesterolaemic hypertensive
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Participant_Condition
hypertensive
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Participant_Condition
lower plasma cholesterol
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Participant_Sex
10 men
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Participant_Age
mean±SD age 58±12 years