Tyagi S C, Smiley L M, Mujumdar V S
Department of Physiology and Biophysics, and Center of Excellence in Cardiovascular-Renal Research, The University of Mississippi Medical Center, Jackson 39216, USA.
Can J Physiol Pharmacol. 1999 Dec;77(12):950-7.
Homocyst(e)ine injured vascular endothelium and modulated endothelial-dependent vascular function. Endothelium plays an analogous role in both the vessel and the endocardium. Therefore, we hypothesized that homocyst(e)ine modulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contractile responses of left and right ventricular rings were measured in an isometric myobath, using different concentrations of CaCl2. The response was higher in the left ventricle than right ventricle and was elevated in endocardium without endothelium. The half effective concentration (EC50) and maximum tension generated by homocyst(e)ine were 10(6) and 5-fold lower than endothelin (ET) and angiotensin II (AII), respectively. However, in endothelial-denuded endocardium, homocyst(e)ine response was significantly increased (p<0.005, compared with intact endothelium) and equal to the response to ET and AII. To determine the physiological significance of ET, AII, homocyst(e)ine, and endothelial nitric oxide in EE function, cardiac rings were pretreated with AII (10(-10) M) or ET (10(-13) M) and then treated with homocyst(e)ine (10(-8) M). Results suggested that at these concentrations AII, ET, or homocyst(e)ine alone had no effect on cardiac contraction. However, in the presence of 10(-10) M AII or 10(-13) M ET, the cardiac contraction to homocyst(e)ine (10(-8) M) was significantly enhanced (p<0.01, compared with without pretreatment) and further increased in the endocardium without endothelium. The pretreatment of cardiac ring with the inhibitor of nitric oxide, Nomega-nitro-L-arginine methyl ester (L-NAME), increased contractile response to homocyst(e)ine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII and ET in enhancing the cardiac contraction.
同型半胱氨酸损伤血管内皮并调节内皮依赖性血管功能。内皮在血管和心内膜中发挥类似作用。因此，我们推测同型半胱氨酸调节心内膜内皮（EE）依赖性心脏功能。制备来自正常雄性Wistar-Kyoto大鼠的离体心脏环。在等长肌槽中使用不同浓度的氯化钙测量左心室和右心室环的收缩反应。左心室的反应高于右心室，且在无内皮的心内膜中升高。同型半胱氨酸产生的半数有效浓度（EC50）和最大张力分别比内皮素（ET）和血管紧张素II（AII）低10（6）倍和5倍。然而，在去内皮的心内膜中，同型半胱氨酸反应显著增加（与完整内皮相比，p<0.005），且与对ET和AII的反应相当。为了确定ET、AII、同型半胱氨酸和内皮一氧化氮在EE功能中的生理意义，用AII（10（-10）M）或ET（10（-13）M）预处理心脏环，然后用同型半胱氨酸（10（-8）M）处理。结果表明，在这些浓度下，单独的AII、ET或同型半胱氨酸对心脏收缩没有影响。然而，在存在10（-10）M AII或10（-13）M ET的情况下，对同型半胱氨酸（10（-8）M）的心脏收缩显著增强（与未预处理相比，p<0.01），且在无内皮的心内膜中进一步增加。用一氧化氮抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）预处理心脏环增加了对同型半胱氨酸的收缩反应。这些结果表明，同型半胱氨酸损害EE依赖性心脏功能，并与AII和ET协同作用增强心脏收缩。
