Homocyst(e)ine impairs endocardial endothelial function

Homocyst(e)ine injured vascular endothelium and modulated endothelial-depen dent vascular function. Endothelium plays an analogous role in both the ves sel and the endocardium. Therefore, we hypothesized that homocyst(e)ine mod ulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contra ctile responses of left and right ventricular rings were measured in an iso metric myobath, using different concentrations of CaCl2. The response was h igher in the left ventricle than right ventricle and was elevated in endoca rdium without endothelium. The half effective concentration (EC50) and maxi mum tension generated by homocyst(e)ine were 10(6) and 5-fold lower than en dothelin (ET) and angiotensin II (AII), respectively. However, in endotheli al-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, homocy st(e)ine, and endothelial nitric oxide in EE function, cardiac rings were p retreated with AII (10(-10) M) or ET (10(-13) M) and then treated with homo cyst(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 t o 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, N-omega-nitro-L-arginine methyl ester (L-NAME), increased contracti le response to homocyst(e)ine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII a nd ET in enhancing the cardiac contraction.