Pliquett Rainer U, Cornish Kurtis G, Peuler Jacob D, Zucker Irving H
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA.
Circulation. 2003 May 20;107(19):2493-8. doi: 10.1161/01.CIR.0000065606.63163.B9. Epub 2003 Apr 14.
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.
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.
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.
羟甲基戊二酸单酰辅酶A还原酶抑制剂（他汀类药物）已被证明可对慢性心力衰竭（CHF）的预后产生有益影响。我们推测，他汀类药物可对自主神经功能产生影响，这可通过血浆去甲肾上腺素水平、肾交感神经活动（RSNA）的直接记录以及压力反射功能来评估。
对血脂正常的CHF兔给予辛伐他汀或赋形剂治疗。通过以320至340次/分钟的频率持续心室起搏3周来诱导CHF。在给兔植入肾神经电极以及动脉和静脉导管后的2至3天，在清醒状态下采集血样并记录RSNA。在给予硝普钠和去氧肾上腺素后评估压力反射功能。正常兔的平均基线RSNA（±SEM）为19.3±3.8%；CHF兔为39.4±2.9%（P<0.05）；低剂量（0.3mg·kg⁻¹·d⁻¹）辛伐他汀治疗的CHF兔为39.8±8.3%（P<0.05）；高剂量辛伐他汀（3mg·kg⁻¹·d⁻¹）治疗的CHF兔为21.1±4.5%（P=无显著性差异）。血浆去甲肾上腺素也观察到类似数据。在接受3mg·kg⁻¹·d⁻¹辛伐他汀治疗的CHF兔中，与CHF对照组相比，硝普钠诱导的短暂性低血压时心率的压力反射调节恢复正常的比例为66%。
这些是首批数据，表明非降脂他汀类药物的作用包括使CHF中的交感神经输出和反射调节恢复正常。这些反应所涉及的精确神经和细胞途径需要进一步阐明。这一发现可能对CHF的治疗和疾病进展具有重要意义。
