黄芩苷对离体大鼠胸主动脉的舒张作用及机制

研究黄芩苷对大鼠离体胸主动脉环的舒张作用并探讨其可能的机制。记录去甲肾上腺素(NE)和KCl预收缩的大鼠离体主动脉环张力变化,观察黄芩苷的舒血管作用及不同工具药对其影响。实验发现黄芩苷对NE和KCl引起的去内皮和内皮完整大鼠胸主动脉环的收缩均有舒张作用;L-硝基精氨酸甲酯、亚甲蓝不能抑制黄芩苷对大鼠胸主动脉环的舒张作用,吲哚美辛能显著抑制;钾离子通道阻断剂4-氨基吡啶、四乙基胺、BaCl2不能抑制黄芩苷对胸主动脉环的舒张作用,格列苯脲能抑制黄芩苷的舒张作用;无钙环境下,黄芩苷预处理对NE收缩有明显抑制作用。因此,黄芩苷具有浓度依赖性血管舒张作用,此作用具有内皮依赖性和非内皮依赖性特点,内皮依赖性收缩可能与前列环素途径有关,非内皮依赖机制可能与KATP通道及钙离子通道有关。     

四乙酰葛根素对离体大鼠胸主动脉环作用初步研究

目的 观察四乙酰葛根素(Tp)对离体大鼠胸主动脉环的作用以及作用机制。方法 采用大鼠离体胸主动脉环灌流装置,观测四乙酰葛根素对重酒石酸去甲肾上腺素(NA)和氯化钾(KCl)预收缩主动脉环张力的影响。结果 四乙酰葛根素对去甲肾上腺素预收缩主动脉环有明显的舒张作用,与空白对照相比,具有显著性差异(P<0.01);由KCl引起主动脉环预收缩,Tp与空白对照相比,具有统计学差异(P<0.01),对内皮完整血管环的舒张作用明显强于去内皮血管环(P<0.01);Tp对NA在无钙液及正常钙液所致离体血管环收缩的舒张作用不明显(P>0.05)。结论 四乙酰葛根素的舒血管作用与受体依赖性钙通道和电压依赖性钙通道均有关,并且其舒血管作用可能与内皮有一定关系。     

盐酸关附甲素对大鼠血管舒缩功能的影响及其机制

目的研究盐酸关附甲素(guanfu base-A,GFA)对大鼠离体胸主动脉舒缩功能的影响,并探讨其可能机制。方法将SD大鼠胸主动脉分离并制成血管环,分成内皮完整组和去内皮组,采用离体血管环实验,观察GFA对基础状态,氯化钾(KCl)预收缩及苯肾上腺素(phenylephrine,PE)预收缩的血管舒张功能的影响,并结合不同抑制剂及无钙液处理,探讨其舒张血管的可能机制。结果累积浓度的GFA(10-8～10-4mol·L-1)对基础状态或KCl预收缩的有无内皮的血管环的张力均无明显影响(P>0.05);对PE(10-6mol·L-1)预收缩内皮完整的血管有浓度依赖性舒张作用,而与PE预收缩的去内皮组相比,从10-7mol·L-1开始差异有显著性(P<0.01)。一氧化氮合酶抑制剂L-NAME、鸟苷酸环化酶抑制剂亚甲蓝及环氧合酶抑制剂吲哚美辛孵育后,均能明显抑制GFA的扩血管作用(P<0.01);经无钙液及GFA处理后,胸主动脉对PE的反应性降低(P<0.01)。结论 GFA对大鼠胸主动脉的舒张作用主要通过两种途径:内皮依赖性舒张作用的机制主要与NO-GC-cGMP途径及激活环氧合酶有关;非内皮依赖性舒张机制主要与抑制内钙释放有关,与门控钙通道引起的外钙内流无关。     

牛磺酸对大鼠胸主动脉的舒张作用及其机制的研究

目的研究牛磺酸舒血管作用的可能机制。方法记录苯肾上腺素(PE)和KCl预收缩的离体大鼠主动脉环张力变化,观察牛磺酸的舒血管作用及不同工具药对其作用的影响。结果牛磺酸(20~80mmol.L-1)对PE(1μmol.L-1)或KCl(60mmol.L-1)预收缩的大鼠主动脉环均有非内皮依赖的、浓度依赖性的舒张作用。在内皮完整的血管环,左旋硝基精氨酸甲酯(0.1mmol.L-1)对牛磺酸的舒血管作用无明显影响;β-丙氨酸(60mmol.L-1)在PE预收缩的血管环增强牛磺酸的舒血管作用,而在KCl预收缩的血管环则降低牛磺酸的舒血管作用;在KCl预收缩基础上,钾通道阻断剂格列本脲(10μmol.L-1)和四乙胺(10mmol.L-1)明显抑制牛磺酸的舒血管作用,而4-氨基吡啶(1mmol.L-1)和BaCl2(1mmol.L-1)无影响。结论牛磺酸有浓度依赖性的血管舒张作用,此作用不依赖血管内皮,可能与其跨细胞膜转运有关,可能有钙依赖性钾通道和ATP敏感性钾通道的参与。     

四乙酰葛根素对离体大鼠胸主动脉环作用初步研究

目的观察四乙酰葛根素（Tp）对离体大鼠胸主动脉环的作用以及作用机制。方法采用大鼠离体胸主动脉环灌流装置,观测四乙酰葛根素对重酒石酸去甲肾上腺素（NA）和氯化钾（Kcl）预收缩主动脉环张力的影响。结果四乙酰葛根素对去甲肾上腺素预收缩主动脉环有明显的舒张作用,与空白对照相比,具有显著性差异（P〈0．01）;由KCl引起主动脉环预收缩,Tp与空白对照相比,具有统计学差异（P〈0．01）,对内皮完整血管环的舒张作用明显强于去内皮血管环（P〈0．01）;Tp对NA在无钙液及正常钙液所致离体血管环收缩的舒张作用不明显（P〉O．05）。结论四乙酰葛根素的舒血管作用与受体依赖性钙通道和电压依赖性钙通道均有关,并且其舒血管作用可能与内皮有一定关系。     

度洛西汀对大鼠胸主动脉环舒张功能的影响

目的研究度洛西汀(DLX)对血管舒张功能的影响并探讨其作用机制。方法采用离体血管环灌流装置,观察DLX对大鼠胸主动脉环的作用及不同工具药的影响。结果 DLX对KCl(30 mmol.L-1)和NE(1μmol.L-1)预收缩的血管环具有浓度依赖的舒张作用,对内皮完整和去内皮血管环舒张作用无差异,该舒张作用为非内皮依赖性。在KCl预收缩基础上,加入钾通道阻断剂格列苯脲Gli(10μmol.L-1)、四乙胺TEA(10 mmol.L-1)、氯化钡BaCl2(1 mmol.L-1)、四氨基吡啶4-AP(1 mmol.L-1)和5-HT2受体阻断剂赛庚啶(1μmol.L-1)均不能抑制DLX的舒血管效应;α1受体阻断剂哌唑嗪(1μmol.L-1)组对DLX舒血管作用有抑制作用。在无钙液中,DLX可以明显抑制NE和CaCl2收缩血管的作用。结论 DLX能够浓度依赖性的舒张血管,其机制可能与抑制经由血管平滑肌细胞膜VDC和ROC通道的钙离子内流,拮抗α1受体以及抑制胞质内钙离子释放有关。     

补骨脂素和补骨脂酚舒张血管的作用机制研究

目的:探讨补骨脂素和补骨脂酚舒张血管的作用机制。方法:取大鼠胸主动脉制备离体血管环及去内皮血管环。采用血管收缩率为考察指标,分别以一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯(L-NAME,100μmol/L)预孵育内皮完整或去内皮血管环后,考察低、中、高剂量补骨脂素或补骨脂酚(0.1、1、10μmol/L)对去甲肾上腺素(NE,1μmol/L)或氯化钾(KCl,60 mmol/L)预收缩血管环的舒张作用;分别以钙依赖型钾离子通道抑制剂氯化四乙胺(TEA,0.1 mmol/L)、内向整流型钾离子通道抑制剂氯化钡(BaCl2,0.1 mmol/L)预孵育去内皮血管环后,考察低、中、高剂量补骨脂酚(0.1、1、10μmol/L)对NE(1μmol/L)预收缩去内皮血管环的舒张作用。采用胶原酶-中性蛋白酶混合消化法分离大鼠心脏微血管内皮细胞,采用酶联免疫吸附法考察低、中、高剂量补骨脂素或补骨脂酚(0.1、1、10μmol/L)对细胞中内皮型一氧化氮合酶(eNOS)蛋白表达的影响。结果:各剂量补骨脂素和补骨脂酚均能显著降低NE预收缩的内皮完整血管环收缩率(P<0.01),中、高剂量补骨脂素和补骨脂酚能显著降低KCl预收缩的内皮完整血管环收缩率(P<0.05或P<0.01),而去内皮和抑制一氧化氮合酶后血管环收缩率显著升高(P<0.05或P<0.01);中、高剂量补骨脂酚能显著降低NE预收缩去内皮血管环收缩率(P<0.05或P<0.01),而抑制血管平滑肌内向整流型钾离子通道后血管环收缩率显著升高(P<0.01)。各剂量补骨脂素和补骨脂酚均能显著提高大鼠心脏微血管内皮细胞中e NOS蛋白表达水平(P<0.01)。结论:补骨脂素和补骨脂酚可能通过内皮依赖性的NO途径以及促进内皮细胞中eNOS蛋白表达来发挥血管舒张作用;补骨脂酚还可能通过开放内向整流型钾离子通道这一非内皮依赖途径发挥血管舒张作用。     

硝酸酯类药物阿魏硝胺对猪冠脉血管舒张作用与机制

目的观察硝酸酯类药物阿魏硝胺(FLNT)对猪冠脉血管舒张作用并探讨其可能机制.方法测定FLNT对氯化钾(KCl)、组织胺(His)和乙酰胆碱(ACh)预收缩猪内皮完整和去内皮冠脉血管环张力的影响,比较FLNT、硝酸甘油(NG)和硝酸异山梨酯对冠脉血管的舒张作用;观察鸟苷酸环化酶阻滞剂亚甲蓝对FLNT血管舒张作用的影响以及FLNT对内向整流性、钙离子激活性、电压敏感性和ATP敏感性钾通道钾特异性阻滞剂(氯化钡、四乙胺、4-氨基吡啶和格列苯脲)所致血管张力的影响,研究FLNT对鸟苷酸环化酶和钾通道的作用.结果对于由KCl,His或ACh预收缩内皮完整和去内皮冠脉血管,FLNT均有浓度依赖性(10-4～10-1 mmol·L-1)舒张作用,内皮完整组和去内皮组之间没有显著差异.FLNT使KCl收缩曲线右移,最大张力减小,pD′2的值为3.68;FLNT对KCl预收缩冠脉的舒张程度类似于硝酸异山梨酯.亚甲蓝能明显减弱FLNT对冠脉血管舒张作用,另外,FLNT象尼可地尔一样可显著地降低氯化钡、四乙胺和格列苯脲预收缩血管的张力.结论FLNT对猪冠脉产生浓度依赖性舒张,且为非内皮依赖性,舒张作用类似于硝酸异山梨酯.FLNT作用机制可能其与激活鸟苷酸环化酶,开放钾通道,抑制电压依赖性钙通道和受体操纵性钙通道有关.     

新结构Rho激酶抑制剂对离体胸主动脉血管环舒张作用及机制研究

目的评价2个全新结构小分子Rho激酶抑制剂J35242和J35243对离体大鼠胸主动脉血管环的舒张作用,并探讨其作用机制。方法利用离体大鼠胸主动脉血管环模型,分别用高浓度KCl和去甲肾上腺素(norepinephrine,NE)预刺激,评价化合物的舒张血管活性;通过各种工具药干预,观察化合物舒张血管作用的内皮相关机制、钾通道相关机制和钙离子相关机制。结果 J35242和J35243可以剂量依赖性舒张高浓度KCl和NE预收缩的血管环,并呈现一定的内皮依赖性;L-NAME和亚甲蓝可在一定程度上影响其舒张作用;化合物还明显抑制由细胞内钙释放和外钙内流引起的血管收缩,说明其可能通过阻断钙离子通道发挥舒张血管作用;另外两个化合物可能不是通过开放钾离子通道发挥舒张血管作用。结论 J35242和J35243在体外具有一定的舒张血管作用,并且J35242的作用要强于J35243,其机制可能依赖于血管内皮功能,另外可能与抑制平滑肌细胞钙离子通道,降低细胞内钙离子浓度相关。     

鸟苷对大鼠胸主动脉血管环的舒张作用及机制

目的研究鸟苷对大鼠离体血管环的影响,并探讨其可能的作用机制。方法分离SD大鼠胸主血管环,分成去内皮组和内皮完整组,采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察鸟苷的舒血管作用并探讨不同抑制剂对鸟苷舒张大鼠离体血管环作用的影响。结果鸟苷(10-9～10-5 mol.L-1)对基础状态下或KCl预收缩血管环的张力无影响;对PE预收缩的血管环有内皮依赖性舒张作用;环氧合酶抑制剂吲哚美辛孵育对鸟苷的舒张作用无明显影响;一氧化氮合酶抑制剂L-NAME或鸟苷酸环化酶抑制剂亚甲蓝可阻断鸟苷的血管舒张作用。结论鸟苷对大鼠离体胸主动脉有浓度依赖性舒张作用,其舒张作用可能与NO-GC-cGMP途径相关。     

Vasodilating effects of carbon monoxide

The vasodilator effects of carbon monoxide (CO) were studied in an isolated perfused rat thoracic aorta preparation. Thoracic aortas from male Sprague-Dawley laboratory rats were dissected free of surrounding tissue, cannulated proximally, and tethered to in situ length. The vessels were perfused with oxygenated Krebs-Henseleit (KH) solution at 37 degrees C in a constant flow system with a circumferentially-applied, pulsatile (300/min), basal "systolic" pressure of 100 mm Hg. Aortas were precontracted with high-potassium (K+) or norepinephrine (NE). Changes in perfusion pressure were indicative of changes in vascular resistance induced by the test gas mixtures. Oxygen (O2) content of the perfusate was kept constant, while CO and nitrogen (N2) were altered. CO (2.5, 5 and 10%) dilated both K+-contracted and NE-contracted aortas in a dose-dependent manner. A significant vasodilation in response to 5% CO (24.5% of maximal), but not to 5% N2, was obtained in the K+-contracted aortas. After the endothelium was removed chemically, the aortas continued to dilate in response to CO. These results suggest that CO has a direct vasorelaxant effect on vascular smooth muscle which is nonspecific and is not endothelium-dependent.     

阿托品对大鼠肠系膜动脉的舒张作用及机制

目的研究阿托品的扩血管作用及机制。方法以大鼠肠系膜动脉为标本，考察阿托品对去甲肾上腺素(NE)预收缩血管的舒张作用以及血管内皮细胞、血管平滑肌在该效应中的作用。结果阿托品能显著舒张NE预收缩的完整内皮血管，去内皮后该作用明显降低。L-N^ω-硝基精氨酸甲酯、吲哚美辛、普萘洛尔及格列本脲对阿托品的舒张作用无明显影响。阿托品对KCl的量效曲线及咖啡因缩血管作用均无明显影响，但能浓度依赖性地抑制NE诱导的内钙释放以及经受体操纵性钙通道的外钙内流。结论阿托品有明显的扩血管作用，其通过抑制受体介导的外钙内流和内钙释放而舒张血管。     

Pharmacological characterization of cellular mechanisms of the renal vasodilatory effect of nicotine in rats

Nicotine causes vasodilation in the renal vasculature through as yet unidentified mechanism. This study investigated the role of endothelial and non-endothelial factors in the vasodilatory action of nicotine in the rat isolated kidney. Nicotine vasodilation in phenylephrine-preconstricted perfused kidneys was evaluated in the absence and presence of drugs that interfere with nitric oxide synthase (NOS), K+ channels, cholinergic or adrenergic activity. Nicotine infusion (5 x 10(-5), 1 x 10(-4), and 5 x 10(-4) M) produced concentration-dependent decreases in the renal perfusion pressure, which continued for 20 min with a peak depressor effect observed at approximately 3 min. Nicotine vasodilation was associated with increases in norepinephrine and NO metabolites (nitrite/nitrate, NOx) levels in the renal effluent. Chemical denudation of the endothelium with 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS), or inhibition of NOS (NG-nitro-L-arginine, L-NNA), or guanylate cyclase (methylene blue) almost abolished the renal vasodilatory action of nicotine. Nicotine vasodilation was also significantly attenuated after selective blockade of ATP-sensitive (K(ATP), glibenclamide) or inward rectifier (Kir, BaCl2) K+ channels but remained unaltered after blockade of large-conductance calcium-activated (BKCa, tetraethylammonium, TEA) or voltage-dependent (Kv, 4-aminopyridine) K+ channels. Hexamethonium (ganglionic blocker), propranolol (beta-adrenceptor blocker), guanethidine (adrenergic neuron blocker), atropine (muscarinic antagonist) or the use of kidneys preconstricted with 80 mM KCl reduced the vasodepressor action of nicotine. Finally, exposure to diclophenac or neostigmine had no effect on nicotine vasodilation. Together, these findings implicate endothelial NOS and KATP and Kir channels in the renal vasodepressor effect of nicotine. Further, the sympathetic-dependent NO-mediated neurogenic vasodilation apparently contributes, at least partly, to nicotine vasodilation.     

苦碟子水提取液对大鼠离体胸主动脉环的舒张作用

目的研究苦碟子的内皮依赖性血管舒张作用,并探讨其可能机制。方法采用大鼠离体主动脉环灌流模型,观察累积浓度苦碟子对基础状态、去氧肾上腺素(PE)和氯化钾(KCl)预收缩的内皮完整血管环和去内皮血管环的舒张作用。结果苦碟子水提取液(苦碟子注射液,相当于含苦碟子原材料0.01～10g.L-1)对基础状态的内皮完整血管环和去内皮血管环的张力无影响。对PE预收缩的内皮完整血管环,苦碟子在累积浓度0.03～10g.L-1呈浓度依赖性舒张作用,分别用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(0.1mmol.L-1)和鸟苷酸环化酶抑制剂亚甲蓝(10μmol.L-1)预处理,此作用被抑制,用环氧合酶抑制剂吲哚美辛(10μmol.L-1)预处理亦被抑制。对KCl预收缩的内皮完整血管环和对PE或KCl预收缩的去内皮血管环,苦碟子在累积浓度0.01～10g.L-1无明显舒缩作用。结论苦碟子(0.03～10g.L-1)对主动脉具有内皮依赖性舒张作用。该作用可能是通过血管内皮细胞一氧化氮-鸟苷酸环化酶途径和血管内皮细胞环氧合酶途径介导的。     

Vasorelaxant effect of formononetin in the rat thoracic aorta and its mechanisms

The purpose of the present study was to investigate the effect of formononetin and the related mechanisms on isolated rat thoracic aorta. Formononetin concentration dependently relaxed aortic rings precontracted with norepinephrine (NE, 1 μM) or KCl (80 mM). Pretreatment with formononetin noncompetitively inhibited contractile responses of aortas to NE and KCl. The vasorelaxant effect of formononetin partially relied on intact endothelia, which was significantly attenuated by incubation with N(ω)-nitro-L-arginine methyl ester (100 μM). In endothelium-denuded rings, glibenclamide (10 μM) and tetraethylammonium (5 mM) showed slight reduction in the vasorelaxant effect of formononetin. Moreover, formononetin reduced NE-induced transient contraction in Ca2?-free solution and inhibited the vasocontraction induced by increasing external calcium in medium plus 80 mM KCl. Our results suggested that formononetin induced relaxation in rat aortic rings through an endothelium-dependent manner via nitric oxide synthesis pathway, and also involving an endothelium-independent vasodilatation by the blockade of Ca2? channels. The opening of K? channels might also be one of the mechanisms of formononetin-induced vasorelaxation.     

Vasodilation activity of dipfluzine metabolites in isolated rat basilar arteries and their underlying mechanisms

Identifying the metabolites of a drug has become an indispensable task in the development of new drugs. Dipfluzine (Dip) is a promising candidate for the treatment of cerebral vascular diseases and has 5 metabolites (M1∼M5) in rat urine and liver microsomes, but their biological activity is still unknown. Because selective cerebral vasodilation is a main role of Dip, we investigated the vasodilation of Dip and its 5 metabolites in isolated Sprague-Dawley (SD) male rat basilar arteries preconstricted with high-K⁺ or 5-HT. The results showed that only M1 possessed concentration-dependent inhibitory activity on the vasoconstriction of arteries with or without the endothelium, and M1 has a more potent vasodilatory effect than Dip on both contraction models. Like Dip, the vasodilatory mechanisms of M1 may be not only related to receptor-operated and voltage-dependent calcium ion channels of smooth muscle cells but also to the release of NO and EDHF from endothelial cells and the opening of Ca²⁺-activated K⁺ channels and ATP-sensitive potassium ion channels. Unlike Dip, the vasodilation mechanism of M1 is also related to the opening of voltage-sensitive K⁺ channel. Together with more selectivity to non-VDCC than Dip, this may partially explain why M1 has stronger vasodilatory effects than Dip. The mechanisms of vasodilation of Dip and M1 may result from the combined action of these or other factors, especially blocking non-endothelium dependent non-VDCC and endothelium dependent IK_Ca channels. These results point to the possibility that M1 provides synergism for the clinical use of Dip, which may inform the synthesis of new drugs.     

降钙素基因相关肽对大鼠血管平滑肌细胞CDK2和Cyclin E的影响

目的:研究降钙素基因相关肽(CGRP)对大鼠血管平滑肌细胞中细胞周期蛋白依赖性激酶2(cyclin-dependent kinase 2,CDK2)和细胞周期蛋白E(Cyclin E)的影响,为阐明CGRP抑制血管平滑肌细胞增殖的细胞周期机制提供实验依据。方法:培养大鼠胸主动脉血管平滑肌细胞,分别用CGRP或/和10%FBS处理细胞。噻唑蓝比色法(MTT)观察CGRP对10%FBS诱导大鼠血管平滑肌细胞增殖的影响;流式细胞术分析细胞周期;Western blot检测CDK2和Cyclin E的表达。结果:CGRP能抑制10%FBS诱导的血管平滑肌细胞增殖,升高G0/G1期细胞百分比,降低S+G2+M期细胞百分比,抑制细胞内CDK2和Cyclin E表达。结论:CGRP能通过阻滞细胞周期由G0/G1期进入S期而抑制血管平滑肌细胞增殖,其作用机制可能与降低CDK2和Cyclin E表达有关。     

薤白提取物对兔离体主动脉条的作用

本实验以离体兔主动脉条为标本 ,对薤白 (EA)的扩血管机制进行了探讨 .观察了薤白对去甲肾上腺素 (NE)、氯化钾 (KCl)和氯化钙 (CaCl2 )的剂量 效应曲线的影响及主动脉条的α受体及 β受体的作用 .观察了EA对NE引起的兔主动脉条两种收缩成分的影响 .结果表明EA能舒张已为氯化钙、高钾和去甲肾上腺素收缩的兔主动脉条 ,使NE、KCl、CaCl2 的剂量 效应曲线非平行右移 ,最大效应降低 .EA松弛血管平滑肌的作用不依赖于阻断α受体或 β受体 ,而与戊脉安 (Ver)相似 ,是通过阻断钙通道实现的 .但它们阻断钙通道的方式不同 .EA可能无选择性阻断电位依赖性钙通道和受体操纵性钙通道 .因此EA的扩血管机制与其对钙通道阻断作用有关 .     

Changes in the vascular beta-adrenoceptor-activated signalling pathway in 2Kidney-1Clip hypertensive rats

1. beta-Adrenoceptor (beta-AR)-mediated vasodilation, which plays an important physiological role in the regulation of vascular tone, is decreased in two-kidney, one clip (2K-1C) renal hypertension. In this study, downstream pathways related to vascular beta-AR activation were evaluated in 2K-1C rats. 2. Relaxation responses to isoprenaline, forskolin and 8-Br-cAMP were diminished in aortas without endothelium from 2K-1C when compared to those in normotensive two kidney (2K). Basal adenosine-3',5'-monophosphate (cAMP), as well as isoprenaline-induced increase in cAMP levels, was not different between 2K and 2K-1C aortas. 3. Contractile responses to caffeine, after depletion and reloading of intracellular Ca(2+) stores, were greater in 2K-1C than in 2K. The presence of isoprenaline during the Ca(2+)-reloading period abolished the differences between groups by increasing caffeine contraction in 2K without changing this response in 2K-1C aortas. Inhibition of the sarcolemmal Ca(2+)ATPase with thapsigargin markedly attenuated isoprenaline vasodilation in both 2K and 2K-1C and abolished the differences between groups. 4. Blockade of ATP-sensitive K(+) channels (K(ATP)) channels with glibenclamide significantly decreased isoprenaline vasodilation in 2K-1C without affecting this response in 2K. Both vascular gene and protein expression of protein kinase A (PKA), as well as phosphoserine-containing proteins, were increased in 2K-1C vs 2K rats. 5. In conclusion, decreased isoprenaline vasodilation in 2K-1C hypertensive rats is related to impaired modulation of the sarcolemmal Ca(2+)ATPase activity. Moreover, K(ATP) channels may play a compensatory role on isoprenaline-induced relaxation in renal hypertension. Both Ca(2+)ATPase and K(ATP) channel functional alterations, associated with decreased beta-AR vasodilation, are paralleled by an upregulation of protein kinase A (PKA) and phosphoserine proteins expression.     

高浓度曲马朵通过内皮依赖与非依赖机制诱导家兔主动脉舒张(英文)

AIM: The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings. METHODS: Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine(10~(-5) mol/L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence and absence of endothelium, indomethacin (an inhibitor of cyclooxygenase), N~G-nitro-L-arginine methyl ester (L-NAME, a specific inhibitor of nitric oxide synthase), glibenclamide (an inhibitor of ATP-sensitive potassium channels), tetraethylammonium chloride (TEA, an inhibitor of calcium-sensitive potassium channels), and naloxone (an antagonist of opioid receptors). RESULTS: Tramadol(10~(-4) mol/L and 3×10~(-4) mol/L) caused significant vasodilation in endothelium-intact and endothelium-denuded aortic rings (P<0.05). The relaxation response to tramadol was significantly greater in endothelium-intact rings than in endothelium-denuded rings. Pretreatment of aortic rings with indomethaci