Kurzelewski M, Duda M, Stanley W C, Boemke W, Beresewicz A
Department of Clinical Physiology, Medical Center of Postgraduate Education, Warsaw.
J Physiol Pharmacol. 2004 Mar;55(1 Pt 1):27-38.
Evidence indicates that nitric oxide (NO) suppresses myocardial oxygen consumption (MVO(2)) and regulates myocardial substrate oxidation, however data from in vivo and isolated heart preparations are conflicting. In addition, cardiac endothelin (ET-1) release has been shown to increase with inhibition of NO synthase (NOS), however the effects of ET-1 on myocardial energetics is not clear. We employed the isolated rat heart model to assess the role of NO and ET-1 on myocardial function and metabolism. Oxidation of glucose and FFA was measured using [U-(14)C]glucose and [9,10-(3)H]palmitate. NOS inhibition with N(G)-methyl-L-arginine acetate salt (L-NMMA, 50 microM), resulted in an increase in MVO(2) at a given rate of myocardial external workload, and no change in myocardial glucose or FFA oxidation. ET-1 (25 pM), which caused coronary vasoconstriction similar to that produced by L-NMMA, also increased MVO(2) without an effect on cardiac workload, or substrate oxidation, suggesting a role for ET-I in the regulation of myocardial energetics. We assessed also the effect of ET(A)/ET(B) receptor blockade (tezosentan; 5 nM) on MVO(2) and glucose and FFA oxidation and observed no effect, suggesting that basal ET-1 production does not play a role in regulating MVO2 or substrate selection. In conclusion, inhibition of NOS or the addition of ET-1 resulted in an increase in MVO2, but did not affect glucose or FFA oxidation.
有证据表明，一氧化氮（NO）可抑制心肌耗氧量（MVO₂）并调节心肌底物氧化，然而来自体内和离体心脏标本的数据却相互矛盾。此外，已表明心脏内皮素（ET-1）的释放会随着一氧化氮合酶（NOS）的抑制而增加，然而ET-1对心肌能量代谢的影响尚不清楚。我们采用离体大鼠心脏模型来评估NO和ET-1对心肌功能和代谢的作用。使用[U-(¹⁴)C]葡萄糖和[9,10-(³)H]棕榈酸酯测量葡萄糖和游离脂肪酸（FFA）的氧化。用N(G)-甲基-L-精氨酸醋酸盐（L-NMMA，50 μM）抑制NOS，在给定的心肌外部工作负荷速率下导致MVO₂增加，而心肌葡萄糖或FFA氧化无变化。ET-1（25 pM）引起的冠状动脉收缩与L-NMMA产生的相似，也增加了MVO₂，而对心脏工作负荷或底物氧化无影响，提示ET-1在心肌能量代谢调节中起作用。我们还评估了ET(A)/ET(B)受体阻断剂（替唑生坦；5 nM）对MVO₂以及葡萄糖和FFA氧化的影响，未观察到作用，表明基础ET-1的产生在调节MVO₂或底物选择中不起作用。总之，抑制NOS或添加ET-1会导致MVO₂增加，但不影响葡萄糖或FFA氧化。
