卡托普利对尼古丁所致大鼠血管内皮功能损伤的保护作用

目的:探讨卡托普利对尼古丁损伤大鼠肠系膜动脉内皮依赖性舒张功能的保护作用及其机制。方法:将30只大鼠分为3组,即正常对照组、尼古丁损伤组(2mg·kg-1)、卡托普利组(尼古丁2mg·kg-1+卡托普利3mg·kg-1),4周后检测各组肠系膜动脉环血管舒张率及血清一氧化氮(NO)含量,一氧化氮合成酶(NOS)、超氧化物歧化酶(SOD)活性。结果:尼古丁使肠系膜动脉环血管舒张率明显降低,并伴随血清NO含量及NOS、SOD活性的明显下降(P<0.01或P<0.05);而卡托普利可升高血管舒张率,并且抑制了尼古丁诱导的NO含量及NOS、SOD活性的下降(P<0.01)。结论:卡托普利对尼古丁所致的血管内皮功能损伤具有明显保护作用,该作用可能与其抗氧化、促进内皮细胞合成、释放NO有关。     

Cariporide对糖基化终末产物所致血管内皮损伤的保护作用

目的观察选择性Na /H 交换蛋白1(NHE-1)抑制剂Cariporide对外源性糖基化终末产物(AGEs)所致大鼠血管内皮功能损伤的保护作用。方法将体外制备的糖基化牛血清白蛋白(AGEs-BSA)通过尾静脉注射的方法,1次.d-1,连续4周,诱导大鼠血管功能损伤,治疗组同时给予Cariporide(0.1、1 mg.kg-1.d-1)灌胃。4周后处死动物,取胸主动脉用于血管内皮依赖性舒张功能的检测,主动脉弓做NF-κB-p65免疫组化检测,并测定血清NO及MDA含量。结果大鼠注射AGEs-BSA后,主动脉对乙酰胆碱诱导的内皮依赖性舒张反应明显降低,大鼠血清MDA水平增加,NO水平降低;Cariporide呈剂量依赖性改善AGEs-BSA所致大鼠胸主动脉内皮依赖性舒张反应降低,抑制AGEs-BSA引起的血清MDA浓度升高和血清NO的减少;给予AGEs-BSA后大鼠血管内皮NF-κB活性明显增加,Cariporide能明显抑制AGEs-BSA诱导的NF-κB活化。结论Cariporide对外源性AGEs诱导的大鼠血管内皮功能损伤具有保护作用,其保护作用可能与降低氧化应激、抑制血管内皮细胞的NF-κB活化有关。     

洛伐他汀对低密度脂蛋白损伤血管内皮的保护作用

目的：探讨洛伐他汀对低密度脂蛋白所致血管内皮功能损伤的保护作用及可能的机制．方法：一次性从大鼠舌下静脉注射天然低密度脂蛋白(n-LDL 4mg／kg),在舌下静脉注射n-LDL之前大鼠腹腔注射洛伐他汀(2或4mg／kg),每天一次,连续五天．注射n-LDL后48小时检测乙酰胆碱诱导的血管内皮依赖性舒张(EDR)及血清一氧化氮(N0)、丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活性．结果：一次注射n-LDL导致了EDR、血清NO水平及SOD活性明显降低,MDA的浓度明显增高。预先给予洛伐他汀能明显减轻LDL引起的EDR的抑制和血清NO水平及SOD活性的降低,减少MDA的生成,左旋硝基精氨酸(L-NNA)减弱洛伐他汀对血管内皮的保护作用．结论：洛伐他汀对LDL损伤的血管内皮具有保护作用,可能与保护内皮依赖性松弛因子和抗氧化作用有关。     

2型糖尿病大鼠主动脉内皮细胞氧化损伤及缬沙坦的保护作用

目的探讨2型糖尿病大鼠氧化应激与主动脉内皮细胞损伤的关系,观察缬沙坦对两者的影响。方法SD大鼠,用长期高能量饮食加小剂量注射链脲佐菌素(STZ)的方法复制模型。注射STZ12wk末,将大鼠分为3组:正常组、糖尿病组、缬沙坦治疗组(24mg·kg-1·d-1,灌胃给药8wk)。在注射STZ12和20wk末,检测大鼠的内皮依赖性血管舒张反应及主动脉内皮形态,血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)和一氧化氮(NO)含量,以及主动脉一氧化氮合酶(NOS)基因表达情况。结果①12wk末,糖尿病大鼠主动脉对低浓度乙酰胆碱(ACh)舒张反应减弱,局部内皮隆起,血清SOD、GSH-Px活性增强,MDA和NO含量增加,主动脉iNOS mRNA表达明显上调,eNOS mRNA表达无明显改变。②20wk末,糖尿病大鼠主动脉对各浓度ACh的反应性均减弱,主动脉内皮变性、坏死,血清SOD、GSH-Px活性减弱,MDA含量进一步增加,NO含量下降,主动脉iNOS mRNA表达仍升高,eNOS mRNA表达降低,缬沙坦治疗后能减轻主动脉病变,改善血清SOD、GSH-Px、MDA、NO及主动脉NOS mRNA表达的异常。结论糖尿病大鼠的氧化应激和NO系统的紊乱参与了主动脉病变过程,增强机体抗氧化能力及调节NO生成可能是缬沙坦发挥主动脉保护作用的机制之一。     

卡托普利对糖基化终产物损伤大鼠血管内皮功能的保护作用

目的研究卡托普利对外源性制备的糖基化终末产物损伤大鼠离体胸主动脉环内皮依赖性舒张功能的影响及其机制。方法按文献方法制备糖基化终末产物,采用外源性糖基化终末产物（AGE-BSA）孵育大鼠离体胸主动脉环90 min诱导血管内皮功能的损伤,并观察卡托普利、超氧化物歧化酶和L-精氨酸对糖基化终末产物所致的血管内皮依赖性舒张反应损伤的影响。结果外源性糖基化终末产物孵育大鼠离体胸主动脉环90 min,明显抑制乙酰胆碱诱导的内皮依赖性血管舒张反应（endothelium-dependent relaxation,EDR）。但对硝普钠诱导的内皮非依赖性血管舒张反应没有影响。卡托普利（3、10和30μmol.L^-1）与AGE-BSA共同孵育血管环90 min,浓度依赖性地改善AGE-BSA对血管内皮依赖性舒张反应的损害。依那普利拉、氧自由基清除剂超氧化物歧化酶（superoxidedismutase,SOD,200 U.mL^-1）也可改善AGE-BSA对内皮依赖性血管舒张反应的损害,而L-精氨酸（L-argi-nine,L-Arg,3 mmol.L^-1）却没有明显的保护作用。结论卡托普利对AGE-BSA所引起的血管内皮依赖性舒张反应的损害具有明显的保护作用,该作用可能与其抗氧化作用有关,同时可能是部分巯基依赖性的。     

依达拉奉对LPC所致兔胸主动脉内皮功能的影响及机制

目的探讨依达拉奉(edaravone,Eda)对溶血磷脂酰胆碱(lysophosphatidylcholine,LPC)所致家兔血管内皮损伤的影响及机制。方法家兔胸主动脉环分别与LPC(5 mg.L-1)和Eda(25～100μmol.L-1)单独孵育或共孵育,分别检测乙酰胆碱诱导的内皮依赖性舒张反应和硝普钠诱导的非内皮依赖性舒张反应,血管组织中一氧化氮(nitric oxide,NO)和丙二醛(malonaldehyde,MDA)含量以及超氧化物歧化酶(superoxide dismutase,SOD)的活性。结果 5 mg.L-1LPC孵育血管环30 min,明显抑制了乙酰胆碱诱导的内皮依赖性舒张反应,但没有影响硝普钠诱导的非内皮依赖性舒张反应,降低了血管组织中NO含量和SOD活性而增加了MDA含量。25～100μmol.L-1Eda分别孵育血管环15min,再与5 mg.L-1LPC共同孵育30 min,明显改善LPC所致的血管舒张功能的损害,升高了血管组织中NO含量和SOD活性而降低了MDA含量。结论 Eda对LPC所致的血管内皮依赖性舒张功能的损伤具有明显的保护作用,该效应可能与其抗氧化作用有关。     

卡托普利对大鼠血管内皮功能损伤的保护作用

目的探讨卡托普利对烟碱所致大鼠血管内皮功能损伤的影响及可能机制。方法将30只大鼠分为3组，即正常对照组、烟碱损伤组（2mg／kg，腹腔注射）、卡托普利保护组（烟碱2mg／kg，腹腔注射＋卡托普利3mg／kg，静脉注射），4周后检测各组肠系膜动脉环内皮依赖性舒张（EDR）反应及主动脉一氧化氮（NO）含量，一氧化氮合成酶（NOS）和超氧化物歧化酶（SOD）活性变化。结果烟碱损伤组肠系膜动脉环EDR明显降低，并伴随主动脉NO含量及NOS，SOD活性的下降；卡托普利保护组血管EDR得到了明显改善，并且抑制了烟碱诱导的主动脉NO含量及NOS，SOD活性的下降。结论卡托普利对烟碱所致血管内皮功能损伤有明显保护作用，该作用与其清除氧自由基、促进内皮细胞合成、释放NO有关。     

卡托普利对对氧磷所致血管内皮损伤的保护作用及机制探讨

目的探讨卡托普利对对氧磷(paraoxon)所致血管内皮功能损伤的保护作用及其机制。方法用大鼠离体血管环和培养的人脐静脉内皮细胞(HUVEC)为实验模型,以血管内皮依赖性舒张(EDR)反应、HUVEC的通透性、内皮细胞活力、内皮细胞的形态学改变及生化参数为指标,用对氧磷作为损伤因子,用血管紧张素转化酶抑制剂(ACEI)卡托普利(captopril)作为保护药,观察了对氧磷对内皮的损伤作用及卡托普利的保护作用。用非巯基类ACEI(依那普利拉,enalaprilat)和抗氧化酶为对照,探讨了卡托普利对对氧磷所致血管内皮损伤的保护作用的机制。结果对氧磷(3.63μmol.L-1)与血管环或内皮细胞共孵30 min,显著性地抑制了血管EDR反应和增加了单层内皮细胞的通透性。卡托普利与血管环共孵30 min,剂量依赖性(0.1、1.0、10μmol.L-1)地显减轻了对氧磷(3.63μmol.L-1)对血管EDR的抑制作用、保护了培养的HUVEC中NO的释放。对氧磷和卡托普利对硝普钠(SNP)诱导的非内皮依赖性舒张反应没有影响。卡托普利(10μmol.L-1)显著性地阻滞了对氧磷所致的单层HU-VEC通透性的增加以及内皮细胞活力的降低、保护了超氧化物歧化酶(SOD)活性、阻滞了丙二醛(MDA)浓度的升高。超氧化物歧化酶、过氧化物酶(catalase)有与卡托普利相似的抗对氧磷损伤作用,但依那普利拉对对氧磷所致损伤无明显保护作用,巯基抑制剂(4-羟基汞苯甲酸普罗比妥钠,cystain)能显著性拮抗卡托普利的保护作用。结论对氧磷能直接损伤血管内皮细胞,卡托普利对氧磷所致的血管内皮细胞损伤有显著性保护作用,其机制可能主要依赖于其所含的巯基的抗氧化作用,而非依赖于抑制血管紧张素转化酶。     

卡托普利抗同型半胱氨酸和溶血性磷脂酰胆碱损伤大鼠血管内皮功能

目的　研究卡托普利能否保护同型半胱氨酸(Hcy)和溶血性磷脂酰胆碱 (LPC)在体外直接损伤的大鼠离体胸主动脉内皮功能。方法　用Hcy或LPC孵育大鼠离体胸主动脉环 3 0min诱导血管内皮损伤 ,观察卡托普利对Hcy和LPC损伤血管内皮依赖性舒张反应的影响。结果　Hcy( 0 .3～ 3mmol·L-1)或LPC( 1～1 0 μmol·L-1)呈浓度依赖性地损伤乙酰胆碱诱导的内皮依赖性血管舒张反应 ,但不影响硝普钠诱导的内皮非依赖性血管舒张。卡托普利( 3～3 0 μmol·L-1)预孵育血管环 1 5min,再与Hcy( 1mmol·L-1)共同孵育 3 0min,浓度依赖性改善Hcy对血管内皮依赖性舒张反应的损害。 3 0 μmol·L-1卡托普利也可完全逆转LPC( 3 μmol·L-1)对内皮依赖性血管舒张反应的损害。结论　卡托普利对Hcy和LPC所引起的血管内皮依赖性舒张反应的损害都具有明显的保护作用     

芝麻素对2型糖尿病大鼠主动脉内皮功能的保护作用

目的探讨芝麻素改善2型糖尿病大鼠主动脉内皮功能损伤的作用及可能机制。方法采用长期高脂饮食加小剂量链脲佐菌素(streptozotocin,STZ)建立2型糖尿病大鼠模型。灌服不同剂量芝麻素(120、60 mg.kg-1.d-1)8周后处死动物。离体血管灌流法测大鼠主动脉内皮依赖性舒张反应及NO生物活性,测血清丙二醛(malondialdehyde,MDA)含量和总抗氧化能力(total antioxidative capacity,T-AOC),Western blot测主动脉内皮型一氧化氮合酶(endothelial nitricoxide synthase,eNOS)、硝基酪氨酸(nitrotyrosine,NT)和还原型辅酶Ⅱ(NADPH)氧化酶亚基P47phox蛋白表达。结果与模型组相比,芝麻素(120 mg.kg-1.d-1)组内皮依赖性血管舒张功能增强,NO活性升高;血清MDA含量降低,T-AOC水平升高;主动脉eNOS蛋白表达增高,NT和P47phox蛋白表达降低。结论芝麻素可改善糖尿病大鼠血管内皮功能,其机制与上调血管eNOS表达和减轻NO氧化失活有关。     

Comparison of captopril and enalapril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE inhibitors in high dieted methionine mice

To examine the role of sulfhydryl (-SH) group in improvement of endothelial dysfunction with angiotensin-converting enzyme (ACE) inhibitors in experimental high dose of methionine dieted rats. We compared the effects of Captopril (an ACE inhibitor with -SH group), enalapril (an ACE-inhibitor without -SH group), N-acetylcysteine (only -SH group not ACE inhibitor) on endothelial dysfunction injured by methionine-induced hyperhomocysteinemia (HHcy) in rats. Male Sprague-Dawley rats were divided randomly into seven groups: control group, L-methionine group, low dose Captopril (15 mg/kg), middle dose Captopril (30 mg/kg), high dose Captopril (45 mg/kg), enalapril (20 mg/kg), N-acetylcysteine (200 mg/kg); control group were intragastric gavaged by water and others groups were intragastric gavaged by L-methionine and drugs in water one time every day. Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation of aortic rings were examined. Paraoxonase1 (PON1) and ACE activity, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD) in serum were analyzed. It was found that a single intragastric gavage by L-methionine resulted in inhibition of endothelium-dependent relaxation, markedly increased the serum level of malondialdehyde and decreased the activity of PON1 and SOD, similarly decreased the level of NO in the serum; but had no effects on endothelium-independent relaxation and angiotensin-converting enzyme activity compared with the control group. Given the treatment with three doses of Captopril (15 approximately 45 mg/kg) markedly attenuated inhibition of vasodilator responses to ACh, and eliminated the increased level of malondialdehyde, the decreased level of NO, activity of PON1 and SOD in serum by single intragastric gavaged L-methionine. However, there were some significant differences among Captopril (30 mg/kg or 45 mg/kg), enalapril (20 mg/kg), and N-acetylcysteine particular in the activity of PON1 and ACE. These results suggested that Captopril can protect the vascular endothelium against the damages induced by L-methionine in rats, and the beneficial effects of Captopril may be related to attenuating the decrease in PON1 activity and NO levels. Furthermore, this protective effect may be concerned with the sulfhydryl group.     

Impairment of endothelium-dependent relaxation of rat aortas by homocysteine thiolactone and attenuation by captopril

To explore the effects of angiotensin-converting enzyme (ACE) inhibitors on endothelial dysfunction induced by homocysteine thiolactone (HTL). Both endothelium-dependent relaxation and nondependent relaxation of thoracic aortic rings in rats induced by acetylcholine (Ach) or sodium nitroprusside (SNP) and biochemical parameters including malondialdehyde (MDA) and nitric oxide (NO) were measured in rat isolated aorta. Exposure of aortic rings to HTL (3 to 30 mM) for 90 minutes made a significant inhibition of endothelium-dependent relaxation induced by Ach, decreased contents of NO, and increased MDA concentration in aortic tissue. After incubation of aortic rings with captopril (0.003 to 0.03 mM) attenuated the inhibition of endothelium-dependent relaxation (EDR) and significantly resisted the decrease of NO content and elevation of MDA concentration caused by HTL (30 mmol/L) in aortic tissues, a similarly protective effect was observed when the aortic rings were incubated with both N-acetylcysteine (0.05 mM). Treatment with enalaprilat (0.003 to 0.01 mM) made no significant difference with the HTL (30 mM) group regarding EDR, but enalaprilat (0.03 mM) and losartan (0.03 mM) could partly restore the EDR in response to HTL (30 mM). Captopril was more effective than enalaprilat and losartan in attenuation of the inhibition of on acetylcholine-stimulated aortic relaxation by HTL in the same concentration. Moreover, superoxide dismutase (SOD, 200 U/mL), which is a scavenger of superoxide anions, apocynin (0.03 mM), which is an inhibitor of NADPH oxidase, and l-Arginine (3 mmol/L), a precursor of nitric oxide (NO), could reduce HTL (30 mM)-induced inhibition of EDR. After pretreatment with not only the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester (L-NAME, 0.01 mM) but also the free sulfhydryl group blocking agent p-hydroxymercurybenzoate (PHMB, 0.05 mM) could abolish the protection of captopril and N-acetylcysteine, respectively. These results suggest that mechanisms of endothelial dysfunction induced by HTL may include the decrease of NO and the generation of oxygen free radicals and that captopril can restore the inhibition of EDR induced by HTL in isolated rat aorta, which may be related to scavenging oxygen free radicals and may be sulfhydryl-dependent.     

Protective effects of ACE inhibitors on vascular endothelial dysfunction induced by exogenous advanced oxidation protein products in rats

To explore detrimental effects of advanced oxidation protein products-bovine serum albumin (BSA) on endothelial function and compare the favorable effects of angiotensin-converting enzyme (ACE) inhibitors: captopril and enalapril. Male Sprague-Dawley rats were randomly divided into groups: control, advanced oxidation protein products-BSA, captopril (10, 20 mg/kg/day), enalapril (15 mg/kg/day), and N(G)-nitro-l-arginine methyl ester (l-NAME, 300 mg/kg/day) plus captopril (20 mg/kg/day) groups. All animals were given advanced oxidation protein products-BSA (100 mg/kg/day, i.v.) except for control group (iv. equal volume of PBS). Rats in other groups were received different drugs intragastrically after advanced oxidation protein products-BSA administration. Endothelium-dependent relaxation of thoracic aorta was assayed. Content of nitrite/nitrate (NO), malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and of ACE in Sera, as well as renal function index including blood urea nitrogen and creatinine were measured. After 30 days, the endothelium-dependent relaxation of blood vessels in received advanced oxidation protein products-BSA rats was significantly impaired compared with control rats. The impairment was accompanied by decreases of serum NO, activity of GSH-Px and SOD. Administration of captopril and enalapril not only decreased damage of endothelium-dependent relaxation, but also reverse the changes of MDA levels, NO content and activity of SOD. The protective effect of captopril was abolished by L-NAME. Blood urea nitrogen and creatinine had no significant differences between various groups. ACE activities were decreased in high captopril and enalapril groups, but did not significantly change in other groups. The results suggested that captopril and enalapril have similar effects on endothelial dysfunction induced by advanced oxidation protein products-BSA, which indicated that protective effects of captopril are not related to sulfhydryl group.     

A reduction of endogenous asymmetric dimethylarginine contributes to the effect of captopril on endothelial dysfunction induced by homocysteine in rats

We examined whether captopril exerts beneficial effect on homocysteine-induced endothelial dysfunction in vivo and whether this effect of captopril is associated with a reduction of endogenous inhibitor of nitric oxide synthase (NOS) asymmetric dimethylarginine (ADMA) in rats. Male Sprague-Dawley rats were given intravenous injections of homocysteine (10 mg/kg/day) to induce endothelial dysfunction. Captopril treatment (3 mg/kg/day, i.v.) was taken in some rats after homocysteine administration. Endothelium-dependent relaxation was tested in aortic rings. Serum levels of ADMA, nitrite/nitrate, malondialdehyde (MDA), and creatinine were measured. Furthermore, superoxide dismutase activity in liver and angiotensin converting enzyme activity in serum were also assayed. Administration of homocysteine to rats for 4 weeks significantly impaired endothelium-dependent relaxation compared with control rats. This impairment of endothelium-dependent relaxation was accompanied by elevated serum concentration of ADMA and decreased serum content of nitrite/nitrate. Moreover, serum concentration of MDA was remarkably increased, whereas liver superoxide dismutase activity was decreased in homocysteine-treated group compared with control. Chronic captopril treatment not only improved the impaired endothelium-dependent relaxation, but also prevented the elevation of serum ADMA and MDA levels, as well as reduction of serum nitrite/nitrate contents and liver superoxide dismutase activity. Serum angiotensin converting enzyme activity and creatinine had no significant difference between the three groups. These results suggest that chronic captopril treatment reduces endogenous inhibitor of NOS in rats with homocysteine injection, which may contribute to the beneficial effect of captopril on homocysteine-induced endothelial dysfunction in vivo, and may be secondary to the antioxidative action of captopril.     

卡托普利对甘油诱导的急性肾衰的保护作用及其机制探讨

目的研究卡托普利对甘油诱导的横纹肌溶解性急性肾衰的保护作用及其机制。方法用50%（v/v）的甘油按8mL.kg^-1后肢肌内注射建立急性肾衰的动物模型。所有大鼠单笼饲养,药物处理组每日分别以卡托普利和依那普利灌胃共7d,第7d损伤组和药物处理组禁水24h后注射甘油,注射甘油后饮水不限,24h后处死动物。通过检测血浆晚期氧化蛋白产物（AOPP）水平、肾组织形态学变化、超氧化物歧化酶（SOD）、血管紧张素转换酶（ACE）和谷胱甘肽过氧化物酶（GSH-Px）活性等查明AOPP是否与急性肾衰有关,并阐明卡托普利对其的保护作用及其机制。结果给大鼠后肢肌内注射50%（v/v）的甘油能诱导横纹肌溶解性急性肾衰,降低SOD、GSH-Px的活性和NO浓度,升高血尿素氮（BUN）、肌酐（Cr）浓度、AOPP和脂质过氧化产物（MDA）水平。卡托普利（30mg·kg^-1）能减轻肾损害和改善肾功能,逆转SOD、GSH-Px的活性、NO和AOPP水平的改变,而依那普利（30mg·kg^-1）和低剂量的卡托普利（10mg·kg^-1）保护作用不明显。结论卡托普利（30mg·kg^-1）对横纹肌溶解所致急性肾衰具有明显的保护作用,该作用可能与其抗氧化作用有关,而且可能是巯基依赖性的。     

Protective effects of cariporide on endothelial dysfunction induced by high glucose

Aim: To explore the effects of cariporide, a selective sodium-hydrogen antiporter inhibitor, on endothelial dysfunction induced by high glucose. Methods: Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were measured in rat isolated aorta. Results: A 6-h incubation of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1μmol/L) with high glucose, cariporide prevented the inhibition of EDR caused by high glucose in concentration-dependent manners. Similarly, high glucose decreased SOD activity and contents of NO, and increased MDA concentration in aortic tissue. Cariporide (1 μmol/L) significantly resisted the decrease of NO content and SOD activity, and elevation of MDA concentration caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1μmol/L) alone had no effect on EDR, endothelium-independent relaxation and biochemical parameters. Conclusion: Cariporide significantly prevented endothelial dysfunction induced by high glucose. The mechanisms of endothelial dysfunction induced by high glucose may involve the activation of sodium-hydrogen antiporter and the generation of oxygen-free radicals, but it is not related to the change of osmolarity.     

EFFECT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS CAPTOPRIL AND ENALAPRIL ON cAMP CONTENT OF SPECIFIC BRAIN AREAS IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The influence of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on the cAMP content of microdissected brain areas was examined in spontaneously hypertensive rats. Both drugs depleted systolic arterial blood pressure significantly. 2. Captopril and enalapril increased the level of cAMP in catecholaminergic cell groups in the lower brain-stem. Captopril was more effective in the substantia nigra, while enalapril treatment resulted in high cAMP levels in the ventrolateral medulla oblongata (A1 catecholaminergic cell group). 3. Both drugs, especially captopril, depleted cAMP content in the cingulate cortex. 4. No changes in cAMP levels were measured in the primary baroreceptor centre (nucleus of the solitary tract) following either captopril or enalapril treatment.