Simvastatin normalizes autonomic neural control in experimental heart failure

Rainer U. Pliquett, Kurtis G. Cornish, Jacob D. Peuler, Irving H Zucker

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Background - HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. Methods and Results - Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (±SEM) in normal rabbits was 19.3±3.8%; in CHF rabbits, 39.4±2.9% (P<0.05); in CHF rabbits on low-dose (0.3 mg · kg-1 · d-1) simvastatin, 39.8±8.3% (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg · kg-1 · d-1), 21.1±4.5% (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg · kg-1 · d-1 simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66% compared with CHF controls. Conclusions - These are the first data showing that non-lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.

Original languageEnglish (US)
Pages (from-to)2493-2498
Number of pages6
JournalCirculation
Volume107
Issue number19
DOIs
StatePublished - May 20 2003

Fingerprint

Simvastatin
Heart Failure
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Rabbits
Baroreflex
Kidney
Nitroprusside
Norepinephrine
Neural Pathways
Phenylephrine
Hypotension
Reflex
Disease Progression
Electrodes
Catheters
Heart Rate

Keywords

  • Baroreceptors
  • HMG-CoA
  • Heart failure
  • Norepinephrine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Simvastatin normalizes autonomic neural control in experimental heart failure. / Pliquett, Rainer U.; Cornish, Kurtis G.; Peuler, Jacob D.; Zucker, Irving H.

In: Circulation, Vol. 107, No. 19, 20.05.2003, p. 2493-2498.

Research output: Contribution to journalArticle

Pliquett, Rainer U. ; Cornish, Kurtis G. ; Peuler, Jacob D. ; Zucker, Irving H. / Simvastatin normalizes autonomic neural control in experimental heart failure. In: Circulation. 2003 ; Vol. 107, No. 19. pp. 2493-2498.
@article{45684f09b50349899c7c1f33c378e687,
title = "Simvastatin normalizes autonomic neural control in experimental heart failure",
abstract = "Background - HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. Methods and Results - Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (±SEM) in normal rabbits was 19.3±3.8{\%}; in CHF rabbits, 39.4±2.9{\%} (P<0.05); in CHF rabbits on low-dose (0.3 mg · kg-1 · d-1) simvastatin, 39.8±8.3{\%} (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg · kg-1 · d-1), 21.1±4.5{\%} (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg · kg-1 · d-1 simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66{\%} compared with CHF controls. Conclusions - These are the first data showing that non-lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.",
keywords = "Baroreceptors, HMG-CoA, Heart failure, Norepinephrine",
author = "Pliquett, {Rainer U.} and Cornish, {Kurtis G.} and Peuler, {Jacob D.} and Zucker, {Irving H}",
year = "2003",
month = "5",
day = "20",
doi = "10.1161/01.CIR.0000065606.63163.B9",
language = "English (US)",
volume = "107",
pages = "2493--2498",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "19",

}

TY - JOUR

T1 - Simvastatin normalizes autonomic neural control in experimental heart failure

AU - Pliquett, Rainer U.

AU - Cornish, Kurtis G.

AU - Peuler, Jacob D.

AU - Zucker, Irving H

PY - 2003/5/20

Y1 - 2003/5/20

N2 - Background - HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. Methods and Results - Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (±SEM) in normal rabbits was 19.3±3.8%; in CHF rabbits, 39.4±2.9% (P<0.05); in CHF rabbits on low-dose (0.3 mg · kg-1 · d-1) simvastatin, 39.8±8.3% (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg · kg-1 · d-1), 21.1±4.5% (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg · kg-1 · d-1 simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66% compared with CHF controls. Conclusions - These are the first data showing that non-lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.

AB - Background - HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. Methods and Results - Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (±SEM) in normal rabbits was 19.3±3.8%; in CHF rabbits, 39.4±2.9% (P<0.05); in CHF rabbits on low-dose (0.3 mg · kg-1 · d-1) simvastatin, 39.8±8.3% (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg · kg-1 · d-1), 21.1±4.5% (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg · kg-1 · d-1 simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66% compared with CHF controls. Conclusions - These are the first data showing that non-lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.

KW - Baroreceptors

KW - HMG-CoA

KW - Heart failure

KW - Norepinephrine

UR - http://www.scopus.com/inward/record.url?scp=0037504350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037504350&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000065606.63163.B9

DO - 10.1161/01.CIR.0000065606.63163.B9

M3 - Article

C2 - 12695293

AN - SCOPUS:0037504350

VL - 107

SP - 2493

EP - 2498

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 19

ER -