Arakawa J, Hara A
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Pharmacology. 1999 Nov;59(5):239-48. doi: 10.1159/000028326.
The present study was carried out to determine the effect of 5-(N, N-dimethyl)-amiloride (DMA), a specific inhibitor of the Na(+)/H(+) exchanger, on the cardiac mechanical and metabolic derangements induced by palmitoyl-L-carnitine (PALCAR). Rat hearts were perfused aerobically at a constant flow according to the Langendorff technique, while being paced electrically. PALCAR (5 micromol/l) increased the left-ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e. mechanical dysfunction), decreased the tissue level of ATP and increased the tissue level of AMP (i.e. metabolic change). DMA (10 or 20 micromol/l) attenuated the mechanical and metabolic alterations induced by PALCAR in a concentration-dependent way. Nevertheless, DMA (10 or 20 micromol/l) did not affect the mechanical function or energy metabolism in the normal (PALCAR-untreated) heart. These results suggest that inhibition of the Na(+)/H(+) exchanger with DMA is effective in attenuating the PALCAR-induced mechanical and metabolic derangements in the heart.
本研究旨在确定钠氢交换体特异性抑制剂5 -（N，N -二甲基）氨氯吡咪（DMA）对棕榈酰-L-肉碱（PALCAR）诱导的心脏机械和代谢紊乱的影响。大鼠心脏按照Langendorff技术在有氧条件下以恒定流量灌注，同时进行电起搏。PALCAR（5微摩尔/升）增加左心室舒张末期压力，降低左心室发展压力（即机械功能障碍），降低组织ATP水平并增加组织AMP水平（即代谢变化）。DMA（10或20微摩尔/升）以浓度依赖的方式减轻了PALCAR诱导的机械和代谢改变。然而，DMA（10或20微摩尔/升）对正常（未用PALCAR处理）心脏的机械功能或能量代谢没有影响。这些结果表明，用DMA抑制钠氢交换体可有效减轻PALCAR诱导的心脏机械和代谢紊乱。
