左旋氨氯地平对颈动脉内膜-中膜厚度及血管内皮功能的影响

目的研究左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度(IMT)及血管内皮依赖性舒张功能的影响。方法共入选90例确诊高血压患者,每天服用左旋氨氯地平2.5mg,进行12个月随防。采用高分辨率超声技术,检测降压治疗前后的颈动脉IMT,并观察静息状态下反应性充血后肱动脉内径变化。结果完成12个月随防的85例高血压患者,左旋氨氯地平治疗降压疗效明显,颈动脉IMT明显减低,从治疗前的(0.95±0.06)mm减低到治疗后的(0.86±0.07)mm(P<0.05),肱动脉内皮依赖性舒张功能(FMD)较治疗前明显改善(P<0.05)。结论左旋氨氯地平降压疗效显著,能延缓颈动脉IMT进展,改善血管内皮功能。     

左旋氨氯地平对颈动脉内膜-中膜厚度及血管内皮依赖性舒张功能的影响

目的观察左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度（CIMT）及血管内皮依赖性舒张功能的影响。方法采用高分辨率超声技术,检测原发性高血压患者93例左旋氨氯地平（2．5—5mg／d）治疗前后CIMT的变化,并观察休息状态、反应性充血后肱动脉内径变化。结果左旋氨氯地平治疗12个月后,降压疗效明显,CIMT明显降低,肱动脉内皮依赖性舒张功能明显改善（P〈0．05）。结论左旋氨氯地平降压疗效显著,能延缓CIMT进展,改善血管内皮依赖性舒张功能。     

左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度及血管内皮依赖性舒张功能的影响

目的观察左旋氨氯地平对高血压患者颈动脉内膜-中膜厚度（CIMT）及血管内皮依赖性舒张功能的影响。方法采用高分辨率超声技术，检测93例原发性高血压患者左旋氨氯地平（2．5～5mg／d）治疗前后CIMT的变化，并观察休息状态、反应性充血后肱动脉内径变化。结果左旋氨氯地平治疗12个月后，降压疗效明显，CIMT明显降低，肱动脉内皮依赖性舒张功能明显改善（P〈0．05）。结论左旋氨氯地平降压疗效显著，能延缓CIMT进展，改善血管内皮依赖性舒张功能。     

NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响

目的考察NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响。方法22wk龄自发性高血压大鼠(SHR)和正常血压WKY大鼠,采用尾套法测定血压,Greiss反应测定血清一氧化氮分泌量,ABTS和FRAP法进行血清总抗氧化能力测定,血管环舒缩测定来评价超氧阴离子清除剂超氧化物歧化酶(SOD)和NADPH氧化酶抑制剂夹竹桃麻素(Apo)对大鼠腹主动脉内皮依赖性舒张反应;采用RT-PCR考察内皮型一氧化氮合酶(eNOS)、NADPH氧化酶亚基p22phox以及NADPH氧化酶亚基gp91phox类似物nox4mRNA表达。结果与WKY大鼠相比,SHR血压升高,而血清总抗氧化水平及NO分泌量均降低。PCR显示SHR胸主动脉中eNOS及p22phoxmRNA表达与WKY大鼠相比差异无显著性,而nox4表达则升高。SHR腹主动脉内皮依赖性舒张反应与WKY相比降低,SOD或Apo均能明显逆转该变化。结论结果提示SHR体内氧化应激状态与NADPH氧化酶gp91phox类似物nox4mRNA过表达有关;NADPH氧化酶依赖性的氧化应激参与了SHR内皮功能障碍的发生发展;药理调节NADPH氧化酶功能或应用抗氧化治疗可明显改善SHR内皮依赖性舒张反应。     

Urocortin舒张自发性高血压大鼠胸主动脉与NO和K~+通道的关系

目的探讨Urocortin(Ucn)对自发性高血压大鼠(SHR)胸主动脉舒缩功能的作用及机制。方法采用体外血管灌流,观察Ucn对SHR胸主动脉的舒张作用,以及左旋硝基精氨酸甲酯(N(ω)n itro-L-argin ine methyl ester,L-NAME)、亚甲蓝(M ethylene B lue,MB)和格列本脲(G lybenc lam ide)对其舒张作用的影响。结果Ucn(1 nmol.L-1~1μmol.L-1)可明显舒张内皮完整和去内皮SHR胸主动脉(P<0.01),此作用具有剂量依赖性;一氧化氮(NO)合成酶抑制剂L-NAME(100μmol.L-1)和鸟苷酸环化酶(GC)抑制剂MB部分抑制Ucn舒张血管的作用,而且增强去甲肾上腺素(NE)产生的收缩反应。ATP敏感钾通道(KATP)阻断剂格列本脲(10μmol.L-1)可减弱Ucn的舒血管作用。结论Ucn对SHR血管具有内皮依赖性和非内皮依赖性舒张作用,此作用部分是Ucn增加血管内皮细胞NO水平实现的,并且与NO-cGMP通路和KATP通道有关。     

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。     

牛磺酸对肾性高血压大鼠主动脉肥厚 与组织局部肾素 血管紧张肽系统的影响

［摘要］目的探讨牛磺酸对肾血管性高血压大鼠主动脉肥厚及组织局部肾素 血管紧张肽系统（RAS）的影响。方法Wistar大鼠60只，随机分为3组，每组20只：假手术对照组、高血压对照组、牛磺酸治疗组。采用两肾一夹型肾血管性高血压大鼠模型。牛磺酸治疗组于术后第5周开始，灌胃给予牛磺酸50 mg·kg 1·d 1。采用标准尾套法间接检测清醒大鼠血压。给药8周后处死大鼠，分离其胸主动脉以用于检测胸主动脉的血管紧张肽Ⅱ含量(放射免疫法检测)、血管紧张肽转换酶活性(分光光度计法检测)和胸主动脉中膜厚度及中膜截面积。结果与假手术对照组大鼠相比，高血压对照组大鼠血压明显升高，胸主动脉的血管紧张肽Ⅱ含量增加，血管紧张肽转换酶活性增高，主动脉中膜厚度及中膜截面积明显增大。应用牛磺酸治疗后则明显抑制大鼠血压的升高，降低胸主动脉的血管紧张肽Ⅱ含量和血管紧张肽转换酶活性，并缩小主动脉中膜厚度及中膜截面积。结论长疗程牛磺酸治疗可抑制肾性高血压大鼠主动脉肥厚的发生，其机制可能与抑制主动脉组织局部血管紧张肽Ⅱ生成有关。     

糖尿病大鼠内源性ADMA升高与代谢控制的关系

目的　以链脲佐菌素诱导的糖尿病大鼠为实验模型 ,研究内源性一氧化氮合酶 (NOS)抑制物非对称性二甲基精氨酸 (ADMA)升高与糖尿病代谢控制的关系。方法　用高效液相色谱测定大鼠血清ADMA浓度 ;用离体胸主动脉环检测乙酰胆碱诱导的内皮依赖性舒张反应 ;并检测血糖、糖基化血清蛋白和血清脂质过氧化产物丙二醛 (MDA)浓度以反映代谢控制。结果　糖尿病大鼠血清ADMA浓度比正常组大鼠明显升高 ,并伴有离体血管内皮依赖性舒张反应的显著抑制 ;经胰岛素治疗 8wk后 ,不仅阻止内源性ADMA的升高 ,也明显改善血管的内皮依赖性舒张功能。此外 ,糖尿病大鼠血糖、糖基化血清蛋白和血清MDA水平也比正常组明显升高。用胰岛素改善代谢控制后 ,血糖、糖基化血清蛋白和血清MDA水平均恢复正常 ,血中ADMA浓度也显著降低。结论　糖尿病大鼠血中内源性NOS抑制物ADMA浓度升高与代谢控制密切相关 ;胰岛素逆转糖尿病大鼠内源性ADMA升高可能与纠正代谢紊乱和降低脂质过氧化有关     

芝麻素对肾性高血压伴高血脂大鼠主动脉舒张功能的影响

目的:探讨芝麻素(Sesamin,Ses)改善肾性高血压伴高血脂大鼠(Rrenal hypertensive-hy-perlipidemia rat,RHHR)主动脉舒张功能损伤的作用机制.方法:RHHR灌服不同剂量Ses(100、33、10 mg·kg-1·d-1)8周后,测定主动脉环对乙酰胆碱(Acetylcholine,ACh)和硝普钠(Sodium nitroprusside,SNP)的舒张反应;测定一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(N-ni-tro-L-arginine-methyl-ester,L-NAME)孵育后,动脉环对ACh的反应并计算一氧化氮(Nitric oxide,NO)活性.结果:与假手术组相比,RH-HR主动脉Ach和SNP诱导的舒张反应显著降低,NO活性减少,Ses治疗8周后能逆转上述作用.结论:Ses降压作用与改善RHHR主动脉内皮依赖性和非内皮依赖性舒张功能损伤有关.     

一氧化氮合酶抑制剂(L-NAME)的药理作用与慢性血管效应

目的:探讨Nω-硝基L-精氨酸甲酯(L-NAME)对不同动脉的慢性血管效应及其与抑制内皮依赖性一氧化氮(EDNO)合成的关系.方法:采用大鼠离体动脉环的张力测定,一氧化氮合酶活性测定及组织学、生化学等方法.结果:给药8周后大鼠尾动脉压明显升高、体重及胸主动脉的内皮依赖性舒张功能明显下降并释放内皮依赖性收缩因子,肠系膜微动脉的内皮依赖性舒张功能无改变.给药8周后出现了动脉中膜肥厚及其周围纤维化.Nω-硝基D-精氨酸甲酯(D-NAME)的慢性给药亦可引起与L-NAME同样的动脉周围纤维化.结论:L-NAME对大鼠胸主动脉及肠系膜微动脉的作用不同,其慢性血管效应与抑制EDNO合成以外的其它机制相关.     

The vasorelaxant effect of hydrogen sulfide is enhanced in streptozotocin-induced diabetic rats

Hydrogen sulfide (H₂S) is an endogenous gas which has potent relaxant effect in vascular and nonvascular smooth muscles. In the present study, we have investigated how streptozotocin (STZ)-induced diabetes affected the relaxant effect of H₂S in rat isolated thoracic aorta and mesenteric and pulmonary arteries. Diabetes was induced by IV injection of STZ (35 mg/kg). Insulin treatment was applied by using insulin implants. At the end of 4 and 12 weeks, the thoracic aorta and mesenteric and pulmonary arteries were isolated, and the relaxation responses to sodium hydrogen sulfide (NaHS), diazoxide, and acetylcholine were evaluated. The mRNA and protein levels of H₂S-synthesizing enzymes were also examined by RT-PCR and Western Blot. The relaxation response to NaHS in the arteries isolated from both 4 and 12 week-diabetic rats was increased when compared with that obtained from the control group. Glibenclamide inhibited the relaxation response to NaHS in the arteries isolated from either diabetic or non-diabetic group of rats. Concurrent treatment of insulin to STZ-injected rats prevented the potentiation of the relaxant effect of NaHS in the arteries. However, acetylcholine and diazoxide-induced relaxation responses were not altered in diabetic group of rats. The mRNA and protein levels of H₂S-synthesizing enzymes were also not altered in diabetic rats. STZ-induced experimental diabetes in rats resulted in the potentiation of the relaxation response to H₂S in vascular tissues. The potentiated relaxation to H₂S in diabetic arteries may play a role in vascular complications frequently seen in severe diabetes.     

海带多糖对愤怒心理应激大鼠血管舒缩功能影响的实验研究

目的研究海带多糖对愤怒心理应激大鼠动脉环舒缩功能的影响。方法将大鼠分为对照组、模型组、海带多糖低剂量组(LP-L)、海带多糖高剂量组(LP-H)及低分子肝素组,造模大鼠通过愤怒心理应激建立内皮损伤模型。造模后各组大鼠进行旷场实验并制备胸主动脉环,分别记录血管在累积浓度乙酰胆碱(ACh)、去甲肾上腺素(NE)诱导后的舒缩反应,以及NO合成酶抑制剂(L-NAME)孵育后累积浓度硝酸甘油及NE对血管舒缩反应的影响。结果模型组、LP-L、LP-H和肝素组旷场实验得分明显高于对照组。与对照组比较,模型组对ACh诱导的血管舒张反应明显减弱,对NE诱导的血管收缩反应明显增强;与模型组比较,LP-H对ACh诱导的血管舒张反应明显增强,对NE诱导的血管收缩反应明显减弱,LP-L和肝素组血管舒缩反应无明显变化。L-NAME孵育后,模型组、LP-L、LP-H和肝素组对硝酸甘油引起的舒张反应与对照组比较均明显减弱,对NE诱导的血管收缩反应均明显增强。但是与模型组比较,LP-H、LP-L对NE引起的血管收缩反应明显减弱,对硝酸甘油引起的舒张反应无明显变化。肝素组血管舒缩反应与模型组比较无明显变化。结论海带多糖对愤怒心理应激大鼠的血管舒缩功能具有一定的调节作用。     

依那普利对2型糖尿病大鼠肠系膜血管内皮细胞的保护作用

目的　糖尿病血管病变的初始原因是血管内皮细胞损害。本研究观察依那普利对糖尿病大鼠肠系膜血管内皮细胞是否有保护作用。方法　大鼠用高脂饮食饲养 4周后 ,ip链佐霉素 30mg·kg- 1诱导 2型糖尿病 ,继续饲以高脂饮食 4周后 ,依那普利组给予依那普利 10mg·kg- 1·d- 1,ig ,连续 4周。采用大鼠离体肠系膜血管灌流技术 ,用去甲肾上腺素 1μmol·L- 1预收缩血管 ,再给予乙酰胆碱 (ACh) 1μmol·L- 1使血管舒张。观察ACh的舒张率来反映内皮细胞功能。结果　糖尿病大鼠肠系膜血管ACh舒张率为 (33±8) % ,较对照组 (79± 8) %明显降低 ,依那普利治疗组血管ACh舒张率为 (5 2± 6 ) % ,较糖尿病组明显改善。用皂素去内皮后 ,三个组肠系膜血管对ACh舒血管的反应性均明显降低 ,三组间无显著性差异。去内皮前后 ,三个组肠系膜血管对硝普钠舒张血管的反应性无显著变化。结论　依那普利对 2型糖尿病大鼠肠系膜血管内皮细胞具有保护作用。     

L-精氨酸对高肺血流所致肺血管结构重建的调节

目的　探讨L 精氨酸 (L Arg)对高肺血流所致肺血管结构重建的作用及其机制。方法　 2 0只Sprague Dawley大鼠随机分为对照组 (n =6 )、分流组 (n =7)和分流 +L Arg组 (n =7)。对分流组和分流 +L Arg组大鼠行腹主动脉 -下腔静脉分流术。对分流 +L Arg组大鼠每天予L Arg 1g·kg-1灌胃。 11wk后 ,以右心导管法测定肺动脉平均压(mPAP) ;检测右心室 /左心室 +室间隔 (RV/LV +S)比值 ;观测肺血管显微和超微结构的变化 ;免疫组织化学方法检测肺动脉人类尾加压素II(hUII)的表达。结果　分流组大鼠mPAP和RV/LV +S比值明显高于对照组 (P均 <0 0 1) ,并且肺动脉显微和超微结构发生明显改变。分流组大鼠肺动脉内皮细胞和平滑肌细胞hUII表达明显增强。分流 +L Arg组大鼠mPAP和RV/LV +S比值明显低于分流组 (P均<0 0 5 )。L Arg缓解了肺血管结构重建的形成 ,同时明显抑制了分流大鼠肺动脉hUII的表达。结论　L Arg抑制肺动脉内皮细胞和平滑肌细胞新型血管活性肽hUII表达 ,可能参与高肺血流所致肺血管结构重建及肺动脉高压的调节     

内源性硫化氢对高肺血流大鼠肺血管重构及血管活性物质的影响

目的探讨内源性硫化氢(hydrogen sulfide,H2S)对大鼠高肺血流性肺血管结构重建及血管活性肽的影响。方法♂SD大鼠32只随机分为分流组、分流+PPG(炔丙基甘氨酸,内源性H2S合成酶的抑制剂)组、对照组和对照+PPG组,每组8只。经腹主动脉-下腔静脉穿刺建立动物模型。分流4wk后,应用敏感硫电极法测定大鼠肺组织硫化氢(H2S)含量;应用放免试剂盒测定血浆中内皮素(ET-1)、心钠素(ANP)、降钙素基因相关肽(CGRP)及肾上腺髓质素(ADM)的含量;观察肺小血管的显微结构变化;结果分流4wk后,大鼠肺组织H2S水平升高,肺血管结构重建,血浆ET-1、ANP、CGRP及ADM升高。PPG干预后,肺组织H2S水平降低,肺血管结构重建加重,血浆ET-1、ANP、CGRP升高,而ADM降低。结论内源性H2S对高肺血流性肺血管结构重建具有重要的保护作用,并对多种血管活性肽具有调节作用。     

埃他卡林对长期低氧大鼠肺组织eNOS mRNA和蛋白表达的影响

目的研究长期低氧对大鼠肺组织eNOS mRNA及蛋白表达的影响及新型ATP敏感性钾(KATP)通道开放剂埃他卡林(iptakalim,IPT)的作用。方法SD♂大鼠60只,随机分成对照组、低氧组、IPT低剂量组(IPT0.75mg.kg-1.d-1,ig)、IPT高剂量组(IPT1.5mg.kg-1.d-1,ig),每组15只。将低氧组、IPT低剂量和高剂量组大鼠放入常压低氧舱内[O2(10%±0.5%)],每周6d,每天8h,4wk后测定平均肺动脉压(mPAP)、RV/(LV+S)和血浆NO浓度。采用RT-PCR技术,分析各组肺组织eNOS mRNA表达;采用Western blot技术,分析各组肺组织eNOS蛋白表达。结果①低氧组大鼠mPAP和RV/(LV+S)高于对照组,IPT低剂量组和高剂量组较低氧组下降,P均<0.05。②低氧组大鼠血浆NO浓度低于正常对照组,IPT低剂量和高剂量组较低氧组上升,P均<0.05。③低氧组eNOS mRNA及蛋白水平均低于对照组(P<0.05),IPT低剂量和高剂量组eNOS高于低氧组(P<0.05),其中高剂量组更加明显。结论长期低氧导致肺血管内皮细胞功能障碍,NO生成减少、eNOS mRNA和蛋白水平表达下降,而IPT可改善内皮细胞功能障碍,增加eNOS的表达和NO的释放,逆转低氧性肺动脉高压。     

COMPARISON OF VASOPRESSOR EFFECTS OF NITRO ARGININE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR-KYOTO RATS

1. NG-nitro-L-arginine (NO2Arg) is a guanidine nitro arginine derivative and an inhibitor of endothelium-dependent vascular relaxation. Significant rise of the systolic blood pressure was observed after 1 week administration of NO2Arg in food (0.023% in weight, about 2.8 mg of NO2Arg/rat per day) in female rats of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). The rises were not different between SHRSP (21 mmHg) and WKY (23 mmHg). 2. In ring preparations of the thoracic aorta of NO2Arg-administered rats of both strains, relaxation by acetylcholine decreased markedly compared with those of the control rats (to 43-44%). On the contrary, glyceryltrinitrate-induced relaxation was slightly but significantly increased in the aorta of WKY after NO2Arg administration and the same tendency was observed in SHRSP. 3. The rise of blood pressure and the decrease of acetylcholine-induced relaxation suggested that NO2Arg inhibited the endothelium-dependent relaxation not only in WKY but also in SHRSP. The relaxation of the thoracic aorta preparation of SHRSP by acetylcholine was much less (ca 38%) than that of WKY; however, that of SHRSP by glyceryltrinitrate was slightly less (ca 74%), indicating that endothelium-dependent relaxation declined in vascular preparation of SHRSP. 4. The present results suggest that endothelium-dependent relaxation has some contribution on blood pressure regulation in the hypertensive state, although a decline of endothelium-dependent relaxation is evident in vascular preparation of SHRSP compared with WKY.     

Erythropoietin administration in vivo increases vascular nitric oxide synthase expression

This study was designed to determine whether recombinant human erythropoietin (rHuEpo) administration increases vascular nitric oxide (NO) production in healthy rats. We hypothesized that rHuEpo hypertension is associated with increased endothelial expression of nitric oxide synthase and augmented NO-dependent vasodilation. Male rats were instrumented with pulsed Doppler flow probes around their ascending aorta and with arterial and femoral catheters. Rats were treated for 14 days with rHuEpo (2 U/d) or vehicle. rHuEpo elevated hematocrit and increased mean arterial pressure (142 +/- 3 versus 116 +/- 4 mm Hg). Thoracic aorta segments from rHuEpo rats had a modest increase in NO-dependent relaxation assessed by acetylcholine (10(-10) to 10(-5) mol/L) relaxation of phenylephrine (PE) (10(-6) mol/L) contracted arteries. Relaxation to NO-donor, s-nitrosyl acetylpenicillamine, and PE contraction were not different from control arteries. The NO synthase inhibitor, N-omega-nitro-L-arginine, increased blood pressure and total peripheral resistance more in rHuEpo rats at both 10 and 30 mg/kg. NOS expression in rHuEpo aorta and plasma NOx concentrations were increased compared with control. Thus, it appears that vascular eNOS expression is increased and causes basal vasodilation in rHuEpo hypertensive rats.     

Effects of sulphite supplementation on vascular responsiveness in sulphite oxidase-deficient rats

1. The aim of the present study was to explore the effect of dietary sulphite supplementation on vascular responsiveness in sulphite oxidase (SO)-deficient rats. 2. Male albino rats were divided into four groups, namely control (n = 8), sulphite-treated (n = 8), SO-deficient (n = 8) and sulphite-treated SO-deficient (n = 8) groups. Sulphite oxidase deficiency was induced by administration of a low-molybdenum diet with concurrent addition of 200 p.p.m. tungsten in the form of sodium tungstate in the drinking water for 9 weeks. Sulphite, in the form of sodium metabisulphite (Na(2)O(5)S(2); 25 mg/kg) was given in the drinking water to sulphite-treated and sulphite-treated SO-deficient groups for the last 6 weeks. The vascular responsiveness of isolated aortic rings to acetylcholine (ACh), sodium nitroprusside (SNP) and histamine was investigated in organ baths. 3. The responsiveness of aortic rings to SNP and histamine did not differ significantly between groups. Conversely, there was a significant decrease in ACh-induced relaxation in aortic rings from the sulphite-treated SO-deficient group compared with the control group (pD(2) 6.2 +/- 0.3 and 7.5 +/- 0.1, respectively; P < 0.05). Incubation of aortic rings in the presence of either l-arginine or superoxide dismutase significantly improved the ACh-induced vasorelaxation in sulphite-treated SO-deficient group (pD(2) 7.2 +/- 0.3 and 7.4 +/- 0.3, respectively). 4. The findings of the present study suggest that the increased production of reactive oxygen species and the resultant increment in l-arginine/nitric oxideconsumption may play a role in the reduced endothelium-dependent vasorelaxation in sulphite-treated SO-deficient rats.     

Rilmenidine prevents blood pressure increase in rats with compromised nitric oxide production

AIM: To search tools of high blood pressure in the model of nitric oxide (NO)-defective hypertension, and thestudy focused on the effect of rilmenidine, agonist of imidazoline receptors, which was suggested to modulatecentral sympathetic outflow. METHODS: Three experimental groups, each consisting of 7 rats, were used: (I) ratswith inhibition of NO synthase (NOS) by Nr-nitro-L-arginine methyl ester (L-NAME) 40 mg.kg-~.d~ for 4 weeks indrinking water, (II) rats with inhibited NOS as in group I, plus agonist of imidazoline receptors rilmenidine 3mg.kg^-1.d^-1 for 4 weeks by garage, and (Ⅲ) control rats. Systolic blood pressure was measured weekly noninvasively.At the end of experiment aortic ring isometric tension was followed, NOS expression (aorta, left ventricle), andNOS activity (left ventricle and brain) were determined. RESULTS: In the group I systolic blood pressure in-creased significantly, aortic ring relaxation to acetylcholine was significantly attenuated. Rilmenidine administeredsimultaneously with L-NAME (group II) prevented the increase of blood pressure which did not differ significantlyfrom control values; aortic ring relaxation to acetylcholine did not differ from control. No change in NOS expres-sion (aorta and left ventricle) was found in groups I and II. Significant decline in NOS activity (left ventricle andbrain) was found in groups I and II. CONCLUSION: Rilmenidine has a remarkable role in NO-defective hypertension,possibly by inhibiting central sympathetic outflow and by affecting receptors in vascular smooth muscle also. Theprime cause of hypertension in this experimental model - the compromised production of NO due to inhibition ofNOS - was not affected by rilmenidine.