The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation o...The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation of rat thoracic aorta, in response to sulfur dioxide (SO2) derivatives “1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3)” using PowerLab tissue bath system. Endothelial denudation enhanced relaxation responses of SO2 derivatives with an IC50 of 6.11 mM as compared to control rings with an IC50 of 6.21 mM, as well as the maximum relaxation (Emax) was increased from 62.026% ± 6.527% to 83.13% ± 14.755%. Furthermore, the relaxation responses to SO2 derivatives in aortic rings were significantly enhanced by indomethacin, clotrimazole and methylene blue with IC50’s of 4.8 mM, 5.33 mM and 4.01 mM, and Emax were raised to 101.1% ± 6.537%, 66.92 ± 7.538 and 104.68 ± 3.575, respectively. Meanwhile, L-NAME did not alter dose-dependent relaxation of SO2 derivatives in comparison to control aortic rings. The results of this study had shown that endothelium denudation and blocking of endothelium derived-relaxation factors enhanced vasodilator effect of SO2;this may clarify the role of endothelium in the vasodilatory mechanism of SO2.展开更多
Based on the EDRF(endothelium derived relaxing factor)-like effects for polyarginine Arg-Arg-oH was selected as the lead compound and its derivatives Arg-Arg- OCH_3.Arg Arg-Arg-OH,HO-ArgCOCH_2CH_2COArg-OH,HO-ArgCOCH_2...Based on the EDRF(endothelium derived relaxing factor)-like effects for polyarginine Arg-Arg-oH was selected as the lead compound and its derivatives Arg-Arg- OCH_3.Arg Arg-Arg-OH,HO-ArgCOCH_2CH_2COArg-OH,HO-ArgCOCH_2COArg-OH,were synthesized.These substances showed on bioassay various degrees of vasorelaxant activities. With protection for the C-terminal of Arg-Arg-OH with a methyl ester.the vasorelaxing ac- tivitv was decreased.In contrast.when the N-terminal of Arg-OH was protected with mal- onic acid or butane diacid.the biological activites were lower than those of Arg-Arg-OH due to the lowered metabolic rate.With protection of N-terminal of Arg-Arg-OH with L-Arg residue.Arg-Arg-Arg-OH was obtained,which showed a vasorelaxing activity better than that of Arg-Arg-OH.The bioactivities observed on the Wister's rats for the former com- pound become the experimental basis for prodrug design of EDRF.展开更多
Direct observation was made by using the patch-clamp technique with a specially designed microperfusion system to investigate the effect of acetylcholine (Ach 10^(-6) mol/L) elicited endothelium-derived relaxing facto...Direct observation was made by using the patch-clamp technique with a specially designed microperfusion system to investigate the effect of acetylcholine (Ach 10^(-6) mol/L) elicited endothelium-derived relaxing factor (EDRF) on the calcium-activated potassium channel (IK(Ca))in the smooth muscle cells of mesenteric resistance vessels in Wistar rats. Activation of IK(Ca) was firstly observed by inducing the elicited EDRF or sodium nitroprusside (SNP 10^(-8) mol/L) under various clamping voltages in cell-attached configuration. While the pipette solution contained KCl 126 mmol/L and the bath solution contained KCl 5.9 mmol/L, two types of conductances of calcium-activated potassium current being 76.4±2.3 pS(mean±S.E. n = 7) and 160.3±7.5 pS (mean±S.E. n= 7) were recorded during the EDRF activation, one type of conductance being 100.5±2.8 pS (mean±S.E. n = 6) was activated by nitric oxide (NO) which is an effective component from SNP. Differences in kinetic characteristics of these channels between EDRF and NO activation were found, particularly the probability of the channel being open in EDRF activation was obviously greater than that in NO stimulation. It has been shown that the potassium channel mechanisms involved in the EDRF and NO actions might be different.展开更多
内皮细胞衍生的舒张因子 (EDRF)的发现及其化学本质、生物合成及生理功能的阐明 ,对心血管病研究产生深远影响。大量试验表明 ,EDRF为NO或R O NO ,病理条件如高血压、动脉粥样硬化、心力衰竭等都有内皮细胞受损 ,表现为EDRF的储备或基础...内皮细胞衍生的舒张因子 (EDRF)的发现及其化学本质、生物合成及生理功能的阐明 ,对心血管病研究产生深远影响。大量试验表明 ,EDRF为NO或R O NO ,病理条件如高血压、动脉粥样硬化、心力衰竭等都有内皮细胞受损 ,表现为EDRF的储备或基础EDRF减少。作为EDRF供体的硝基类血管扩张剂可以补充心血管病理状态下EDRF的不足 ,对人类心血管疾病的临床治疗。展开更多
文摘The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation of rat thoracic aorta, in response to sulfur dioxide (SO2) derivatives “1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3)” using PowerLab tissue bath system. Endothelial denudation enhanced relaxation responses of SO2 derivatives with an IC50 of 6.11 mM as compared to control rings with an IC50 of 6.21 mM, as well as the maximum relaxation (Emax) was increased from 62.026% ± 6.527% to 83.13% ± 14.755%. Furthermore, the relaxation responses to SO2 derivatives in aortic rings were significantly enhanced by indomethacin, clotrimazole and methylene blue with IC50’s of 4.8 mM, 5.33 mM and 4.01 mM, and Emax were raised to 101.1% ± 6.537%, 66.92 ± 7.538 and 104.68 ± 3.575, respectively. Meanwhile, L-NAME did not alter dose-dependent relaxation of SO2 derivatives in comparison to control aortic rings. The results of this study had shown that endothelium denudation and blocking of endothelium derived-relaxation factors enhanced vasodilator effect of SO2;this may clarify the role of endothelium in the vasodilatory mechanism of SO2.
基金This project was supported by the National Natural Science Foundation of China
文摘Based on the EDRF(endothelium derived relaxing factor)-like effects for polyarginine Arg-Arg-oH was selected as the lead compound and its derivatives Arg-Arg- OCH_3.Arg Arg-Arg-OH,HO-ArgCOCH_2CH_2COArg-OH,HO-ArgCOCH_2COArg-OH,were synthesized.These substances showed on bioassay various degrees of vasorelaxant activities. With protection for the C-terminal of Arg-Arg-OH with a methyl ester.the vasorelaxing ac- tivitv was decreased.In contrast.when the N-terminal of Arg-OH was protected with mal- onic acid or butane diacid.the biological activites were lower than those of Arg-Arg-OH due to the lowered metabolic rate.With protection of N-terminal of Arg-Arg-OH with L-Arg residue.Arg-Arg-Arg-OH was obtained,which showed a vasorelaxing activity better than that of Arg-Arg-OH.The bioactivities observed on the Wister's rats for the former com- pound become the experimental basis for prodrug design of EDRF.
基金Project supported by the National Natural Science Foundation of China.
文摘Direct observation was made by using the patch-clamp technique with a specially designed microperfusion system to investigate the effect of acetylcholine (Ach 10^(-6) mol/L) elicited endothelium-derived relaxing factor (EDRF) on the calcium-activated potassium channel (IK(Ca))in the smooth muscle cells of mesenteric resistance vessels in Wistar rats. Activation of IK(Ca) was firstly observed by inducing the elicited EDRF or sodium nitroprusside (SNP 10^(-8) mol/L) under various clamping voltages in cell-attached configuration. While the pipette solution contained KCl 126 mmol/L and the bath solution contained KCl 5.9 mmol/L, two types of conductances of calcium-activated potassium current being 76.4±2.3 pS(mean±S.E. n = 7) and 160.3±7.5 pS (mean±S.E. n= 7) were recorded during the EDRF activation, one type of conductance being 100.5±2.8 pS (mean±S.E. n = 6) was activated by nitric oxide (NO) which is an effective component from SNP. Differences in kinetic characteristics of these channels between EDRF and NO activation were found, particularly the probability of the channel being open in EDRF activation was obviously greater than that in NO stimulation. It has been shown that the potassium channel mechanisms involved in the EDRF and NO actions might be different.
文摘内皮细胞衍生的舒张因子 (EDRF)的发现及其化学本质、生物合成及生理功能的阐明 ,对心血管病研究产生深远影响。大量试验表明 ,EDRF为NO或R O NO ,病理条件如高血压、动脉粥样硬化、心力衰竭等都有内皮细胞受损 ,表现为EDRF的储备或基础EDRF减少。作为EDRF供体的硝基类血管扩张剂可以补充心血管病理状态下EDRF的不足 ,对人类心血管疾病的临床治疗。