Multiple transforming growth factor-ß (TGF-ß) responsive elements have been identified within the 5’-flanking region of the plasminogen activator inhibitor type-1 (PAI-1) gene. This study was designed to characterize the major TGF-ß responsive element (-804 to -546). DNA footprint assays showed that the region of protein contact (-726 to -703) did not include consensus sequences for any known transacting factors. The results of UV cross-linking and Southwestern blot experiments showed that a protein of M, 100,OOO specifically binds to the TGH-ß responsive element and that this protein undergoes post-transcriptional activation within 5 min after stimulation of Hep G2 cells by TGF-ß resulting in a marked increase in affinity for the target DNA sequence. These results show that stimulation of Hep G2 cells with TGF-ß increases the affinity of a novel pr 100-kDa protein for the major TGF-ß responsive element within the PAI-1 gene.

AIM: To investigate the changes of cardiac calcium handling proteins and endothelin system in dilated cardiomyopathy (DCM) rats and the effects of perindopril and bisoprolol on the remodeling ventricles. METHODS: DCM rats were employed using a 2-kidney, 1-clip hypertensive and diabetic model. Some of the DCM rats were treated with perindopril and bisoprolol for 3 months, respectively. The ratio of left ventricular weight to body weight (LVW/BW), mRNA expressions of calcium handling proteins and endothelin receptors were determined. The alterations of maximum binding capacity (Bmax) and equilibrium dissociation constant (KD) values of cardiac endothelin receptors (ETR) and its subtypes were detected. RESULTS: Compared with those of normal control, blood pressure, and LVW/BW in the DCM rats were elevated. Sarcoplasmic reticulum calcium pump (SERCA) mRNA expression and SERCA activity decreased in the left ventricle. The ETR Bmax decreased, especially the endothelin receptor A. Endothelin converting enzyme activity and expression were elevated, and mRNA expressions of β1-adrenoreceptor and inositol-3-phosphate receptor in some hearts increased as well. The administration of perindopril and bisoprolol could reverse myocardial hypertrophy and restore the imbalance of calcium handling proteins and endothelin system. CONCLUSION: The disorder of calcium handling proteins and endothelin system existed in the hearts of DCM rats. Treatment of perindopril and bisoprolol could reverse myocardial hypertrophy and changes in DCM rats.

目的　全国十二家大型医院协作观察中西医结合治疗急性病毒性心肌炎疗效。方法 对1 028 例临床诊断为急性病毒性心肌炎患者随机各分两组,治疗组602 例,用中西医结合(黄芪、牛磺酸、泛葵利酮、抗心律失常药等) 治疗;对照组426 例,用常规(极化液、抗心律失常药等) 治疗。结果 中西医结合治疗组临床症状改善、外周血肠道病毒阴转、心电图ST2T改变及房室传导阻滞、阵发性心房颤动、窦房传导阻滞等恢复均优于对照组( P < 0. 01、0. 05) ;对早搏及心功能改善两组间无统计学差异( P < 0. 05) 。结论　在目前对急性病毒性心肌炎无特效药物治疗的情况下,采用中西医结合治疗可作为一种治疗手段。

The present study was designed to determine whether or not an increase in endothelial intracellular concentration of calcium ([Ca2+]i) evokes endotheliumdependent contractions in the aorta from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine, adenosine triphosphate (ATP) and the calcium ionophore, A 23187, produced endothelium-dependent relaxations in isolated aortic rings of both WKY and SHR. These relaxations in response to the three agonists were significantly smaller in the SHR when compared with the WKY. Endothelium-dependent contractions to acetylcholine, ATP and A 23187 were observed only in the aorta isolated from the SHR. In the presence of NG-nitro-Larginine, an NO synthase inhibitor, the endothelium-dependent contractions in response to acetylcholine, ATP and A 23187 were potentiated significantly in the aorta SHR and were unmasked in that of WKY. However, the contractions were still significantly greater in SHR than in WKY. These contractions were abolished by indomethacin and valeryl salicylate (two cyclo-oxygenase inhibitors) as well as by S 18886 (a TP-receptor antagonist), indicating that the endothelium-dependent contraction produced by the three agonists share the same characteristics. The results of the present study indicate that the release/generation of endotheliumderived contracting factor, requires an increase in endothelial [Ca2+]i.

A modified bioassay system was designed to demonstrate the diffusible nature of endothelium-derived contracting factor(s) released by acetylcholine in the aorta of spontaneously hypertensive rat. In “sandwich”-like layered preparation, isometric tension was recorded from a bioassay strip (without endothelium) in the presence of NG-nitro-L-arginine and tetrahydrobiopterin to selectively potentiate endothelium-dependent contractions. A donor strip (with or without endothelium) was stitched on the bioassay tissue so that it did not directly contribute to the recorded contractions. Acetylcholine induced contractions that occurred only when the donor strip was with endothelium. Superoxide dismutase did not affect but catalase and the combination of superoxide dismutase plus catalase significantly decreased the endothelium-dependent contraction. The contractions in the layered preparations were abolished when the donor strip with endothelium was treated previously with valeryl salicylate, an irreversible cyclooxygenase-1 inhibitor, but remained unaffected when the bioassay strip was treated with the compound. Previous treatment of the bioassay strip alone with S 18886 abolished the contractile response, whereas treatment of the donor strip with endothelium by the selective TP receptor antagonist only produced a moderate inhibition. These results indicate that in the aorta of spontaneously hypertensive rats, endothelium-dependent contractions to acetylcholine involve a diffusible substance(s) released by the endothelium. The production of this contracting factor(s) requires the activation of endothelial cyclooxygenase-1, and its action the activation of TP receptors on the vascular smooth muscle cells.