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达尔盐敏感大鼠高血压心力衰竭发生过程中心脏代谢的影响。大鼠在6周龄后喂食含有8% NaCl的饲料，导致12周龄时代偿性肥厚，18周龄时导致心力衰竭。代偿性肥厚和心力衰竭大鼠的主要能量底物从游离脂肪酸转变为葡萄糖。然而，在心力衰竭前的肥厚心脏中，脂肪酸的β-氧化受损，胰岛素刺激期间增加心脏葡萄糖摄取的能力显著降低。心力衰竭大鼠心脏摄取脂肪酸减少，β-氧化严重受损。胰岛素刺激不再增加葡萄糖的摄取。依那普利不影响收缩压，但可减轻心力衰竭大鼠左室（LV）功能的恶化（以左室dP/dt/P评估）。依那普利明显改善代偿性肥厚时胰岛素输注时葡萄糖摄取增加的能力。在心力衰竭大鼠中，在胰岛素输注前，依那普利抑制了脂肪酸摄取的减少，并显著增加了基线时的葡萄糖摄取。因此，依那普利对高血压心力衰竭的作用可能，至少部分是由于能量代谢的改变，以更有效的能量产生，即葡萄糖的利用。在我们使用微透析方法的初步研究中，依那普利降低了左室间质去甲肾上腺素的水平。因此，依那普利对交感神经活动的抑制可能有助于心脏能量代谢的这些有利变化。

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.