Chowdhary Saqib, Ng G Andre, Nuttall Sarah L, Coote John H, Ross Hamish F, Townend Jonathan N
Department of Cardiovascular Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, U.K.
Clin Sci (Lond). 2002 Apr;102(4):397-402.
Cardiac parasympathetic control has prognostic significance in heart failure, but the control mechanisms of this system remain poorly defined. We have demonstrated previously a facilitatory role for nitric oxide (NO) in the parasympathetic control of heart rate in young healthy human subjects. In view of the complex abnormalities of regional NO activity observed in chronic heart failure, we now aim to establish if this mechanism is active in subjects with this condition. Groups of 12 heart failure patients [NYHA class II-III; mean age 52 years (range 38-67 years)] and 12 age/sex-matched healthy control subjects [mean age 50 years (range 36-62 years)] were studied. Heart rate variability and baroreflex sensitivity were measured during inhibition of endogenous NO production with N(G)-monomethyl-l-arginine (l-NMMA; 3 mg.h(-1).kg(-1)) and during administration of an equipressor dose of the control vasoconstrictor phenylephrine (12-36 microg.h(-1).kg(-1)). Basal levels of nitrate+nitrite were measured in the plasma as an indication of systemic NO production. In the heart failure patients, despite an equal rise in blood pressure with both drugs, high-frequency indices of heart rate variability increased less with l-NMMA than with phenylephrine: RMSSD (root mean square of successive RR-interval differences) increased by 4+/-2 compared with 26+/-8 ms (P<0.001) and high-frequency power increased by 97+/-62 compared with 1372+/-861 ms(2) (P<0.001). The increases in cross-spectral baroreflex sensitivity were also lower with l-NMMA than with phenylephrine [high-frequency alpha-index, 2.2+/-1.3 and 12.6+/-3.8 ms/mmHg respectively (P<0.001); low-frequency alpha-index, 1.3+/-0.9 and 4.3+/-1.7 ms/mmHg respectively (P<0.05)]. Healthy subjects showed a similar discrepancy in the response of high-frequency indices of heart rate variability to the two drugs, although baroreflex sensitivity responses were significantly different only for the high-frequency alpha-index. Levels of plasma nitrate+nitrite were significantly higher in the heart failure patients compared with controls. These data demonstrate that baroreflex-mediated cardiac parasympathetic activation in human heart failure, as in health, is dependent upon endogenous NO synthesis.
心脏副交感神经控制在心力衰竭中具有预后意义，但该系统的控制机制仍不清楚。我们之前已经证明一氧化氮（NO）在年轻健康人类受试者心率的副交感神经控制中起促进作用。鉴于在慢性心力衰竭中观察到区域NO活性存在复杂异常，我们现在旨在确定该机制在患有这种疾病的受试者中是否活跃。研究了12例心力衰竭患者组[纽约心脏协会（NYHA）II - III级；平均年龄52岁（范围38 - 67岁）]和12例年龄/性别匹配的健康对照受试者组[平均年龄50岁（范围36 - 62岁）]。在用N(G)-单甲基-L-精氨酸（L-NMMA；3 mg·h⁻¹·kg⁻¹）抑制内源性NO生成期间以及给予等压剂量的对照血管收缩剂去氧肾上腺素（12 - 36 μg·h⁻¹·kg⁻¹）期间，测量心率变异性和压力反射敏感性。测量血浆中硝酸盐 + 亚硝酸盐的基础水平作为全身NO生成的指标。在心力衰竭患者中，尽管两种药物引起的血压升高相同，但L-NMMA引起的心率变异性高频指标增加幅度小于去氧肾上腺素：连续RR间期差的均方根（RMSSD）增加4±2，而去氧肾上腺素引起的增加为26±8 ms（P < 0.001）；高频功率增加97±62，而去氧肾上腺素引起的增加为1372±861 ms²（P < 0.001）。L-NMMA引起的交叉谱压力反射敏感性增加也低于去氧肾上腺素[高频α指数分别为2.2±1.3和12.6±3.8 ms/mmHg（P < 0.001）；低频α指数分别为1.3±0.9和4.3±1.7 ms/mmHg（P < 0.05）]。健康受试者在心率变异性高频指标对两种药物的反应中也表现出类似差异，尽管压力反射敏感性反应仅在高频α指数上有显著差异。与对照组相比，心力衰竭患者血浆硝酸盐 + 亚硝酸盐水平显著更高。这些数据表明，与健康状态一样，人类心力衰竭中压力反射介导的心脏副交感神经激活依赖于内源性NO合成。
