Sympathetic nerve activity and cardiac energy metabolism during the development of hypertensive heart failure

研究血管紧张素转换酶抑制剂依那普利对Dahl盐敏感大鼠高血压性心力衰竭形成过程中心脏代谢的影响。这些大鼠在6周龄后喂食含有8%氯化钠的饲料，导致12周龄时出现代偿性肥大，并导致18周龄时心力衰竭。在代偿性肥厚和心力衰竭的大鼠中，主要能量底物从游离脂肪酸转移到葡萄糖。然而，在心力衰竭之前的肥厚心脏中，脂肪酸的β氧化受到损害，在胰岛素刺激期间增加心脏葡萄糖摄取的能力显著降低。在心力衰竭大鼠，心脏对脂肪酸的摄取减少，β氧化损伤更严重。胰岛素刺激不再增加葡萄糖摄取。依那普利不影响收缩压，但可减轻心力衰竭大鼠左心功能的恶化。依那普利显著改善代偿性肥厚时胰岛素输注过程中增加葡萄糖摄取的能力。在心力衰竭大鼠中，依那普利可抑制基础状态下FTFT酸摄取的下降，并显著增加胰岛素输注前的葡萄糖摄取。因此，依那普利治疗高血压心力衰竭的作用可能至少部分源于能量代谢的改变，即更有效的能量产生，即葡萄糖的利用。在我们采用微透析法进行的初步研究中，依那普利降低了左室间质去甲肾上腺素水平。因此，依那普利对交感神经活动的抑制可能与心脏能量代谢的这些有利变化有关。

We studied the effects of enarapril, angiotensin converting enzyme inhibitor, on cardiac metabolism during the development of hypertensive heart failure of Dahl salt sensitive rats. The, rats were fed a diet containing 8% NaCl after the age of 6 weeks that resulted in the development of compensated hypertrophy at 12 weeks of age, leading to heart failure by 18 weeks. Major energy substrate shifted from free fatty acid to glucose in rats with compensated hypertrophy and heart failure. However, β-oxidation of fatty acid was impaired and the capacity to increase cardiac glucose uptake during insulin stimulation markedly reduced in hypertrophied hearts prior to heart failure. In rats with heart failure, cardiac uptake of fatty acid reduced and the β-oxidation was impaired severer. Insulin stimulation did not increase glucose uptake any more.Enarapril did not affect systolic blood pressure but attenuated the deterioration of left ventricular(LV) function assessed by LV dP/dt/P in rats with heart failure. Enarapril markedly improved the capacity to increase glucose uptake during insulin infusion at compensated hypertrophy. In rats with heart failure, enarapril inhibited the decrease in fttfty acid uptake and markedly increased glucose uptake at baseline before insulin infusion.Thus, the effects of enarapril on hypertensive heart failure may, at least in part, result from changes in energy metabolism to more efficient energy production, i.e., glucose utilization. In our preliminary study using a microdialysis method, levels of LV interstitial norepinephrine were reduced by enarapril. Therefore, the inhibition of sympathetic nerve activity induced by enarapril may contribute to these favorable changes in cardiac energy metabolism.