Ahmad A, Sattar M A, Rathore H A, Abdulla M H, Khan S A, Abdullah N A, Johns E J
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Department of Physiology, University College Cork, Cork, Ireland.
J Physiol Pharmacol. 2016 Feb;67(1):31-44.
The present study investigated the role of endothelial nitric oxide synthase (eNOS) enzyme in the development of left ventricular hypertrophy (LVH) in Wistar-Kyoto rats. The effect of L-arginine administration on cardiac structure, arterial stiffness, renal and systemic hemodynamic parameters was studied and the change in expression of eNOS and cystathione γ lyase (CSE) in the myocardium of LVH rats was evaluated. LVH was induced using isoprenaline (5 mg/kg, S.C.) and caffeine (62 mg/L in drinking water) for 14 days. Following to that, L-arginine (1.25 g/L in drinking water) was given for 5 weeks as a donor of NO. eNOS and CSE gene expressions were down regulated in the LVH group by about 35% and 67% respectively when compared to control. However, in the LVH group treated with L-arginine there was up regulation of eNOS by almost 27% and down regulation in CSE by 24% when compared to control (all P < 0.05). Heart index and H2S plasma levels were reduced by almost 53% in the L-arginine treated LVH group compared to the control (all P < 0.05). Mean arterial pressure, heart rate and pulse wave velocity were reduced while renal blood perfusion increased in L-arginine treated LVH rats compared to their untreated counterparts (all P < 0.05). The enhanced expression of eNOS in L-arginine treated LVH rats resulted in the amelioration of oxidative and haemodynamic parameters suggesting that NO system is an important therapeutic target in cardiac and LV hypertrophies.
本研究调查了内皮型一氧化氮合酶（eNOS）在Wistar-Kyoto大鼠左心室肥厚（LVH）发展过程中的作用。研究了给予L-精氨酸对心脏结构、动脉僵硬度、肾脏及全身血流动力学参数的影响，并评估了LVH大鼠心肌中eNOS和胱硫醚γ裂解酶（CSE）表达的变化。使用异丙肾上腺素（5mg/kg，皮下注射）和咖啡因（饮用水中62mg/L）诱导LVH 14天。之后，给予L-精氨酸（饮用水中1.25g/L）作为一氧化氮供体，持续5周。与对照组相比，LVH组中eNOS和CSE基因表达分别下调约35%和67%。然而，与对照组相比，L-精氨酸处理的LVH组中eNOS上调近27%，CSE下调24%（所有P<0.05）。与对照组相比，L-精氨酸处理的LVH组心脏指数和血浆硫化氢水平降低近53%（所有P<0.05）。与未处理的LVH大鼠相比，L-精氨酸处理的LVH大鼠平均动脉压、心率和脉搏波速度降低，而肾血流量增加（所有P<0.05）。L-精氨酸处理的LVH大鼠中eNOS表达增强导致氧化和血流动力学参数改善，表明一氧化氮系统是心脏和LV肥厚的重要治疗靶点。
