Simvastatin normalizes autonomic neural control in experimental heart failure.
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.


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 x kg(-1) x d(-1)) simvastatin, 39.8+/-8.3% (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg x kg(-1) x d(-1)), 21.1+/-4.5% (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg x kg(-1) x 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.
Pliquett
Rainer U
RU
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA.
Cornish
Kurtis G
KG
Peuler
Jacob D
JD
Zucker
Irving H
IH
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D008076:Cholesterol, HDL; D002784:Cholesterol; D019821:Simvastatin; D009638:Norepinephrine