Inhibition of nitric oxide synthase by L-NAME improves ventricular performance in streptozotocin-diabetic rats.
Inhibition of nitric oxide synthase by L-NAME improves ventricular performance in streptozotocin-diabetic rats.
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DOI：
10.1006/jmcc.1997.0474
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发表时间：
1997-09
影响因子：
5
通讯作者：
J. Smith;D. Paulson;F. Romano
中科院分区：
文献类型：
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作者：
J. Smith;D. Paulson;F. Romano
本研究的总体目标是确定一氧化氮合成途径的激活是否会抑制8周链脲佐菌（60 mg/kg，静脉注射）糖尿病（STZ-Db）大鼠的基本心室功能和对心脏功能特征的β -肾上腺素能刺激的反应性。在不存在或不存在一氧化氮合酶（NOS）非选择性抑制剂ng -硝基- l -精氨酸甲酯（L-NAME, 1 mM）的情况下，测量离体工作心脏在0.8 μ m多巴酚丁胺反应前和峰值时的左心室表现。STZ-Db心脏在基础（心率、心输出量、主动脉流量-dP/dt）和多巴酚丁胺刺激（+dP/dt和最大收收压的上升减弱）条件下的心室功能受到抑制。L-NAME对对照心脏基底或多巴酚丁胺刺激的心室功能影响最小。相比之下，STZ-Db灌注L-NAME后，降低的心率恢复到控制值，这与主动脉流量增加有关。此外，多巴酚丁胺刺激的最大收缩压升高和+dP/dt在l-NAME存在下在对照组和STZ-Db大鼠中相似。Western blot检测到STZ-Db大鼠心室肌细胞中存在诱导型一氧化氮合酶（NOS），且组成型NOS显著（P<0.001）升高。这些数据表明，STZ-Db动物心室肌细胞中NOS产生的一氧化氮增加，抑制了糖尿病心脏的基础心室功能和对β -肾上腺素能刺激的反应。
The overall goal of this study was to determine if activation of the nitric oxide synthetic pathway suppressed basal ventricular performance and the responsiveness to beta-adrenergic stimulation characteristic of cardiac function in the 8-week streptozotocin (60 mg/kg, i.v.) diabetic (STZ-Db) rat. Left ventricular performance was measured in isolated working hearts, before and at the peak response to 0.8 microM dobutamine, in the absence or presence of NG-nitro-L-arginine methyl ester (L-NAME, 1 mM), a non-selective inhibitor of nitric oxide synthase (NOS). Ventricular performance was suppressed in the STZ-Db heart under basal (decreased heart rate, cardiac output, aortic flow -dP/dt) and dobutamine-stimulated (diminished rise in +dP/dt and maximum systolic pressure) conditions. L-NAME had minimal effects on basal or dobutamine-stimulated ventricular performance in control hearts. In contrast, L-NAME infusion in hearts from STZ-Db returned the depressed heart rate to control values, which was correlated with an increase in aortic flow. In addition, the dobutamine-stimulated rise in maximum systolic pressure and +dP/dt were similar in the control and STZ-Db rats in the presence of l-NAME. Western blot analysis detected the presence of inducible nitric oxide synthase (NOS) and a significant (P<0.001) increase in the constitutive NOS in ventricular myocytes from STZ-Db rats. These data suggest that an increased production of nitric oxide by NOS in ventricular myocytes from STZ-Db animals suppressed basal ventricular performance and the responsiveness to beta-adrenergic stimulation in diabetic hearts.