Oxidative status and anti-oxidant enzyme activity during calcium paradox in the rat isolated heart

1. The effect of calcium paradox on oxidative status and the activity of anti-oxidant enzymes were studied in the rat isolated heart. Glutathione status, sulphydryl group contents and lipid peroxidation in the myocardium, as well as the release of oxidized and reduced glutathione from the heart, were taken as indices of oxidative events. 2. Reperfusion with calcium after calcium-free perfusion induced a significant decrease in the myocardial content of reduced and oxidized glutathione and non-protein sulphydryl groups. At the same time, a significant release of both forms of glutathione from the heart was observed. However, the ratio of oxidized to reduced glutathione remained unchanged and was not different from control. Increased lipid peroxidation was observed only after 30 min of reperfusion with calcium. 3. Increased anti-oxidant activity during the reperfusion period was observed. Mitochondrial Mn-superoxide dismutase (SOD) activity was increased throughout the reperfusion period, while cytoplasmic Cu,Zn-SOD and glutathione peroxidase activity showed a transient increase at 5 min reperfusion. 4. The results do not support an important role of oxygen free radicals in cell damage observed during calcium paradox in the rat isolated heart. Production of oxygen free radicals may occur during the reperfusion period, but the quantity produced is insufficient to exceed the anti-oxidant capacity of the heart.     

Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight

AIMS: Nitroglycerin (GTN) modulates tissue damage induced by ischaemia and reperfusion (IR) in a mechanism that is similar to ischaemic preconditioning. We set out to study, using a human model of endothelial IR injury, whether GTN-induced endothelial preconditioning is mediated by reactive oxygen species (ROS) formation and/or opening of mitochondrial permeability transition pores (mPTP). METHODS: In two double-blind, randomized, parallel studies, a total of 66 volunteers underwent measurement of radial artery endothelium-dependent, flow-mediated dilation (FMD) before and after local IR. Subjects were treated, 24 h before IR, with different drugs in order to test the mechanism of GTN-induced endothelial protection. RESULTS: Transdermal GTN (0.6 mg h(-1) for 2 h, administered 24 h before IR) significantly reduced the impairment of FMD caused by IR (placebo group: FMD after IR, 1.3 +/- 0.8%; GTN group: FMD after IR, 5.3 +/- 0.9%, P < 0.01 compared with placebo). This protective effect was lost when vitamin C (2 g i.v. at the time of GTN administration) or ciclosporin (an inhibitor of mPTP, 100 mg 2 h prior to GTN administration) were coadministered (FMD after IR: vit C + GTN group, 2.1 +/- 1.0%; ciclosporin + GTN group, 1.7 +/- 0.8%; both P < 0.05 compared with GTN alone). CONCLUSIONS: We demonstrate that GTN protects the endothelium against IR-induced endothelial dysfunction, in an effect similar to delayed ischaemic preconditioning. Using a human model, we provide evidence supporting the concept that this protective effect is mediated by ROS release and mPTP opening upon GTN administration.     

Ischaemia enhances the role of Ca2+-activated K+ channels in endothelium-dependent and nitric oxide-mediated dilatation of the rat hindquarters vasculature

1. We compared the effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (L-NOARG) and tetraethylammonium (TEA), a blocker of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, on vasodilator responses to endothelium-dependent (acetylcholine; ACh) and -independent (sodium nitroprusside; SNP) vasodilators. The mechanism of the vasodilator responses was determined in rat hindquarters under normal conditions (sham ischaemia) and after 2 h ischaemia followed by reperfusion with physiological saline. 2. In sham ischaemia, the responses to ACh were significantly reduced by L-NOARG (1 mmol/L) and TEA (1 mmol/L) and there was a further reduction in response the presence of both agents. Dilator responses to SNP were significantly enhanced by L-NOARG, whereas TEA did not alter the SNP-induced vasodilatation when given either alone or in the presence of L-NOARG. 3. After ischaemia, L-NOARG caused a similar inhibition of ACh-induced dilatation to that observed in sham ischaemia. However, TEA alone or combined with L-NOARG caused a significantly greater inhibition of the ACh-induced vasodilatation after ischaemia than observed in the sham ischaemia group. Tetraethylammonium alone did not affect the responses to SNP, but it did attenuate the enhanced dilatation observed in the presence of L-NOARG. 4. In the rat hindquarters vasculature, both nitric oxide and the opening of TEA-sensitive K(+) channels contribute to ACh-induced endothelium-dependent dilatation. In addition, a TEA-sensitive mechanism was not involved in the SNP-induced dilatation under normal conditions but, after ischaemia, if there is a further inhibition of endogenous nitric oxide by L-NOARG, exogenous nitric oxide causes dilatation that is sensitive, in part, to TEA. Thus, the contribution of the opening of BK(Ca) channels to endothelium-dependent vasodilatation assumes greater importance after ischaemia and reperfusion. This may reflect an increased ability of nitric oxide or cGMP to open BK(Ca) channels after ischaemia.     

白藜芦醇对高脂血症大鼠多种抗氧化系统的影响

<正>近年研究已证实白藜芦醇(resresveratrol,Resv)具有抗肿瘤、抗氧化、抗心血管疾病等作用[1]。Resv抗氧化作用的研究主要集中在其对超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的影响,但Resv对其他抗氧化作用影响的研究较少,本次实验我们观察了白藜芦醇对L-Arg-NO途径及HDL的抗氧化成分——对氧磷酶1(paraoxonase-1,PON1)的表达和活性影响,以便更深入了解白藜芦醇的抗氧化作用机制。     

The opposite effects of nitric oxide donor,S‐nitrosoglutathione,on myocardial ischaemia/reperfusion injury in diabetic and non‐diabetic mice

Nitric oxide is a potent anti‐apoptotic and cardioprotective molecule in healthy animals. However, recent study demonstrates that overexpression of eNOS exacerbates the liver injury in diabetic animals. whether diabetes may also alter NO's biologic activity in ischaemic/reperfused heart remains unknown. The present experiment was designed to determine whether the nitric oxide donor, S‐nitrosoglutathione, may exert different effects on diabetic and non‐diabetic myocardial ischaemia/reperfusion (MI/R) injury. Diabetic state was induced in mice by multiple intraperitoneal injections of low‐dose streptozotocin (STZ). The control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours reperfusion. At 10 minutes before reperfusion, diabetic and non‐diabetic mice were received an intraperitoneal injection of S‐nitrosoglutathione (GSNO, a nitric oxide donor, 1 μmol/kg). GSNO attenuated MI/R injury in non‐diabetic mice, as measured by improved cardiac function, reduced infarct size and decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but, rather, aggravated the MI/R injury in diabetic mice. Mechanically, the diabetic heart exhibited an increased nitrative/oxidative stress level, as measured by peroxynitrite formation, compared with non‐diabetic mice. Co‐administration of GSNO with EUK134 (a peroxynitrite scavenger) or MnTE‐2‐PyP5 (a superoxide dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before reperfusion significantly decreased the MI/R‐induced peroxynitrite formation and the MI/R injury. Collectively, the present study for the first time demonstrated that diabetes may cause superoxide overproduction, increase NO inactivation and peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule to a cardiotoxic molecule.     

骨性关节炎患者血清和关节液中自由基水平及意义

目的 了解骨性关节炎(OA)患者血清和关节液中自由基水平,探讨一氧化氮(NO)和氧自由基在骨性关节炎发生发展中的作用.方法 检测了63例骨性关节炎患者(OA组)和20例健康对照者(对照组)血清和关节液中NO和超氧化物歧化酶(SOD)、丙二醛(MDA)的含量.结果 与对照组比较,OA患者血清中NO和MDA含量显著升高(P＜0.01),SOD含量明显下降(P＜0.05);关节液中NO和MDA含量明显高于血清中的含量(P＜0.01,P＜0.05),SOD含量低于血清中的含量(P＜0.05).结论 OA患者体内自由基水平增高,NO和氧自由基在骨性关节炎的发病机制中具有重要的作用.     

Heat stress increases endothelium-dependent relaxations and prevents reperfusion-induced endothelial dysfunction

1. Heat stress has been widely used to stimulate the expression of stress proteins and is associated with various cardiovascular changes, including anti-ischaemic effects. However, the effect of heat stress on endothelial function is less clear. 2. Heat stress was induced in anaesthetized rats by increasing body temperature to 42 degrees C for 15 min. Twenty-four hours later, segments of rat aorta and mesenteric and coronary arteries were mounted in organ chambers. 3. Heat stress markedly increased relaxation to acetylcholine (ACh) in all three blood vessels studied, without affecting the response to the nitric oxide (NO) donor sydnonimine-1. 4. Heat stress also increased aortic relaxation to histamine and the calcium ionophore A23187. 5. In the aorta, an inhibitor of NO synthesis abolished the response to ACh in both control and heat stressed-rings, whereas a cyclo-oxygenase inhibitor had no effect. 6. Heat stress also prevented completely the impaired response to ACh in coronary arteries isolated from rats subjected to myocardial ischaemia and reperfusion. 7. Thus, heat stress increases the stimulated release of NO the rat aorta and mesenteric and coronary arteries and prevents reperfusion-induced injury at the level of the coronary endothelium.     

大鼠急性脑缺血后脑组织一氧化氮和氧自由基的变化

OBJECTIVEOxygen free radicals and nitric oxide have been proposed to be involved in acute CNS injury produced by cerebral ischemia. However, controversy remains regarding how they cause injury. The present study was designed to explore the changing tenden     

Cardioprotective effects of a non-alcoholic extract of red wine during ischaemia and reperfusion in spontaneously hypertensive rats

1. We reported recently the cardioprotection conferred by a non-alcoholic extract of Cabernet-Sauvignon red wine (RWE) against alterations derived from ischaemia and reperfusion in normotensive rats. The aim of the present study was to assess the effects of RWE on ischaemia/reperfusion injury in hearts isolated from spontaneously hypertensive rats (SHR). 2. After stabilization, rat isovolumic perfused hearts were exposed to a 20 min global ischaemic period followed by 30 min reperfusion in the absence (ischaemic control (IC) hearts) or presence of RWE infused prior to ischaemia and early in reperfusion. In other hearts, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, was administered prior to RWE infusion (L-NAME + RWE). 3. Left ventricular developed pressure (LVDP), dP/dt(max) and left ventricular end-diastolic pressure (LVEDP) were used to assess myocardial function. 4. At the end of reperfusion, LVDP and dP/dt(max) decreased to 47 +/- 9 and 46 +/- 9% of baseline values, respectively, in IC. Treatment with the RWE significantly improved systolic postischaemic recovery (LVDP = 85 +/- 8%; dP/dt(max) = 83 +/- 5%) and attenuated the increase in LVEDP (23 +/- 6 and 53 +/- 8 mmHg in RWE and IC, respectively; P < 0.05). 5. In the L-NAME + RWE group, L-NAME completely abolished the systolic and diastolic protection induced by RWE (LVDP = 44 +/- 13%; dP/dt(max) = 43 +/- 13%; LVEDP = 60 +/- 10 mmHg). 6. These data are the first demonstration that a non-alcoholic extract of Cabernet-Sauvignon red wine protects SHR hearts from systolic and diastolic alterations induced by ischaemia and reperfusion through a nitric oxide-dependent mechanism.     

NO 、NOS、SOD及氧自由基在分泌性中耳炎中耳积液和血清中的表达及意义

目的：探讨一氧化氮(nitric oxide，NO)、一氧化氮合酶(nitric oxide synthase，NOS)、超氧化物歧化酶(superoxide dismutase，SOD)及氧自由基在分泌性中耳炎(secretory otitis media，SOM)发病机制中的作用。方法：对实验性SOM和SOM患者中耳积液和血清中NO、NOS、SOD及氧自由基进行检测，并比较单纯应用抗生素与NO合成抑制荆 抗氧化荆 抗生素治疗SOM后血清中各指标的变化情况。结果：实验性SOM和SOM患者血清中NO、NOS、SOD、MDA含量均明显高于正常对照组。鼓室积液中NO、NOS、SOD、MDA含量均明显高于血清中含量。NO合成抑制荆 抗氧化荆 抗生素治疗SOM后血清NO、NOS、SOD、MDA含量明显低于单纯应用抗生素组，差别有统计学意义。结论：NO、NOS、SOD及氧自由基在分泌性中耳炎发病和转归中起重要作用，N-硝基-L-精氨酸甲酯(L-NAME)、维生素C、维生素E及SOD对SOM的治疗有效。     

银杏叶渣中多糖的提取及其抗氧化活性研究

目的 研究从银杏叶渣中提取多糖的工艺,及其抗氧化活性。方法 以多糖提取率为评价指标,通过苯酚-硫酸法检测,经单因素试验得到最佳工艺,所得银杏多糖进行还原能力和清除DPPH自由基的试验。结果 最佳工艺条件为：料液比1：7,提取时间2h,提取2次,醇沉浓度90%,醇沉1h。银杏多糖具有较强的还原能力和清除DPPH自由基的能力。结论 该工艺简便可行,稳定可靠,适于工业生产,所得多糖具有较强的抗氧化活性。     

玉郎伞黄酮对大鼠心肌缺血再灌注损伤的保护作用

目的探讨玉郎伞黄酮(YF)对大鼠心肌缺血再灌注(MIR)引起的氧化性应激损伤的保护作用。方法60只SD大鼠,随机分为假手术组,MIR组,生理盐水组和YF低、中、高剂量组,每组大鼠10只,雌雄各半。结扎冠状动脉左前降支30 min后,再灌注60 min,建立MIR模型。用不同剂量YF在结扎前30 min分别做预处理。再灌注结束后采血,测定血浆中天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、乳酸脱氢酶同工酶1(LDH1)、超氧化物歧化酶(SOD)和丙二醛(MDA)的改变,测量心肌梗死面积。结果YF预处理能明显降低血浆中AST、LDH、LDH1和MDA含量,能提高SOD活性,降低心肌梗死面积。结论YF对大鼠MIR氧化性应激损伤具有显著的保护作用。     

Impaired effect of salt loading on nitric oxide-mediated relaxation in aortas from stroke-prone spontaneously hypertensive rats

1. The present study was designed to characterize the effects of salt on vasorelaxation via the nitric oxide (NO)/cGMP pathway in stroke-prone spontaneously hypertensive rats (SHRSP), which are highly salt sensitive. 2. Male 8-week-old SHRSP were given 1% NaCl solution as drinking water for 4 weeks, whereas control animals were given water only. 3. In aortic rings from salt-loaded SHRSP, relaxations in response to acetylcholine and sodium nitroprusside were significantly impaired compared with those in the control. In the presence of zaprinast, a cGMP-specific cyclic nucleotide phosphodiesterase (PDE)-5 inhibitor, the cGMP levels induced by these drugs were significantly reduced by salt loading, but remained unchanged in the absence of zaprinast. The protein levels of endothelial NO synthase, soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG) remained unchanged with salt loading, but those of PDE-5 decreased significantly and those of phosphorylated PKG tended to decrease, although the change was not statistically significant. Salt loading significantly impaired the relaxation in response to 8-bromo-cGMP. 4. These results indicate that, in aortas from SHRSP, salt loading causes impairment of relaxation in response to NO, which may be due to a decrease in cGMP production by sGC and impairment of the relaxation pathway downstream of cGMP, which, in turn, probably causes a decrease in PKG activity. Reduced PDE-5 protein expression may act, in part, as a compensatory response to impairment of cGMP-mediated relaxation.     

Vascular non-endothelial nitric oxide induced by swimming exercise stress in rats

1. Herein, we report the effects of acute or chronic forced swimming on vascular responsiveness to angiotensin (Ang) II. 2. The possible involvement of locally produced substances, such as nitric oxide (NO) and prostanoids, in these effects were studied in rat thoracic aorta and superior mesenteric arteries. 3. Chronic, but not acute, swimming reduced the efficacy (maximal effect; Emax) of AngII in thoracic aorta and mesenteric arteries, either with intact or denuded endothelium. 4. The efficacy of AngII was reduced in the presence of indomethacin in mesenteric arteries, but not in the aorta, from either control or chronically stressed rats. 5. Treatment with NG-monomethyl-l-arginine reversed the effect of chronic stress on the response to AngII, suggesting that chronic stress may increase non-endothelial NO activity in both the aorta and mesenteric arteries. 6. The effects of acute and chronic stress on vascular reactivity were selective for AngII because no changes were observed on the effects of phenylephrine.     

Increase in gastric intramucosal hydrogen ion concentration following endotoxin challenge in the rat and the actions of nitric oxide synthase inhibitors

1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxin lipopolysaccharide (LPS) was developed in the rat. The role of nitric oxide (NO) in these events in this model was evaluated using the non-selective NO synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA). 2. The pHi and intramucosal [H+] were evaluated in omeprazole-pretreated rats (30 mg/kg, i.p.) using the Henderson equation after estimating the PCO2 and the bicarbonate concentration in gastric wall. To measure gastric wall PCO2, the oesophagus was intubated and the pylorus ligated. The PCO2 was measured by a blood gas analyser in 2 mL saline instilled for 30 min in the gastric lumen to equilibrate with the gastric wall. The pHi was measured under basal conditions and 3 and 5 h after LPS (3 mg/kg) administration. Separate groups received treatment with L-NMMA (25-50 mg/kg) or L-NAME concomitantly or 2.5 h after administration of LPS. 3. Intravenous administration of Escherichia coli LPS provoked a significant fall in gastric pHi from 7.37 to 7.18 (median values; n =10-19) determined after 5 h. In groups treated concurrently with LPS and L-NAME (5 mg/kg; n = 19), there was a similar increase in intramucosal [H+] as that induced by LPS alone (n = 15) in those animals that survived. In contrast, L-NAME (5 mg/kg; n = 12), given 2.5 h after LPS challenge, at a time at which inducible NOS is known to be significantly expressed, prevented the increase in intramucosal [H+] at 3 and 5 h after LPS challenge. Similarly, L-NMMA (25-50 mg/kg; n = 23), given 2.5 h after LPS challenge, dose-dependently inhibited the increase in intramucosal [H+] at 3 and 5 h. 4. In conclusion, these findings indicate that this rat model could be useful in exploring the pathophysiology of acute endotoxin shock. Delayed administration of L-NAME and L-NMMA abolished the increase in gastric intramucosal [H+], supporting the involvement of excess NO in the tissue dysfunction associated with endotoxin shock. This suggests the potential value of this small animal model in evaluating the therapeutic activity of novel agents for use in septic shock.     

Effect of inhibition of neuronal nitric oxide synthase and L-arginine supplementation on renal ischaemia-reperfusion injury and the renal nitric oxide system

The role of nitric oxide synthases (NOS) and the nitric oxide (NO) substrate l-arginine in renal ischaemia-reperfusion (I/R) has been studied extensively. However, the results reported are often controversial. In the present study, we examined the effects of the neuronal (n) NOS inhibitor 7-nitroindazole (7-NI) and L-arginine administration on renal I/R injury and the renal NO system in rats. Following 7 days pretreatment with 7-NI (50 mg/kg per day), L-arginine (2 g/kg per day) or vehicle (dimethylsulphoxide : sesame oil, 1 : 9), the left renal vascular pedicles were clamped for 50 min in male Sprague-Dawley rats and kidneys were removed 24 h after reperfusion (n = 7/group). Neither 7-NI nor L-arginine had any effect on parameters of renal function, the grade of tissue injury or the number of terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL)-positive tubular cells compared with vehicle-treated rats. 7-Nitroindazole decreased nNOS mRNA expression and inducible (i) NOS protein levels, but had no effect on endothelial NOS expression. L-arginine supplementation increased mRNA expression of all NOS isoforms, but only increased protein expression of iNOS. The results of the present study demonstrate that selective inhibition of nNOS has no effect on renal injury, indicating that nNOS does not play a central role in the pathophysiology of renal I/R. In addition, although L-arginine has no effect on renal I/R injury in the model used in the present study, its administration increases the mRNA expression of NOS isoforms.     

兔肝缺血-再灌注损伤时乳酸脱氢酶活性的变化和左旋精氨酸的保护作用

目的 :探讨兔肝缺血 再灌注损伤 (HIRI)时乳酸脱氢酶 (LDH)活性的变化和左旋精氨酸 (L Arg)的保护作用及其机制。方法 :实验兔 2 1只 ,随机分为对照组、盐水组和L Arg组 ,每组 7只。制作肝缺血 再灌注损伤模型 ,观察血清及肝组织LDH活性、丙二醛 (MDA)浓度、超氧化物歧化酶 (SOD)活性、一氧化氮代谢产物 (NO-2 NO-3)水平的变化及L Arg对它们的影响。结果 :盐水组血清LDH活性进行性升高 (P <0 .0 1 ) ,肝组织内LDH、SOD活性和NO-2 NO-3水平明显下降 (P <0 .0 5 ,P <0 .0 1 ) ,而MDA含量显著增高 (P <0 .0 1 ) ;L Arg组变化不明显 ,与盐水组比较 ,血清及肝组织内LDH、SOD活性、MDA含量及NO-2 NO-3浓度 ,均有显著性差异 (P <0 .0 5或P <0 .0 1 )。结论 :L Arg可通过降低体内氧自由基水平、提高一氧化氮水平 ,对HIRI时LDH活性的异常改变起积极的保护作用     

Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta

1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low-density lipoprotein (LDL) from oxidation. We functionally evaluated the anti-oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations. 2. After native LDL (N-LDL) from rabbit plasma had been pre-incubated in the presence or absence of fluvastatin (10 micromol/L) for 4 h, the N-LDL was mildly oxidized by incubation with 5 micromol/L CuCl2 for 5 h and two oxidized LDL, fluvastatin-pretreated (Flu-OxLDL) and -non-treated (OxLDL), were prepared. The level of thiobarbituric acid-reactive substances (TBARS) in Flu-OxLDL and OxLDL markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 3. When macrophages were incubated with Flu-OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 4. Acetylcholine-induced endothelium-dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu-OxLDL or OxLDL. The degree of impairment was significantly less in Flu-OxLDL. 5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium-dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 micromol/L). 6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti-oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.     

OXYGEN RADICALS AND NITRIC OXIDE IN RAT MESENTERIC ISCHAEMIA-REPERFUSION: MODULATION BY L-ARGININE AND NG-NITRO-L-ARGININE METHYL ESTER

1. The aims of the present study were to detect changes in superoxide anion (O₂^?), nitric oxide (NO) and other reactive oxygen species (ROS) directly by measurement of chemilumin-escence (CL) and to investigate the role of L-arginine, a nitric oxide synthase (NOS) substrate, and N^G-nitro-L -arginine methyl ester (L-NAME), a NOS inhibitor, together with their molecular enantiomers D-arginine and D-NAME, in a rat mesenteric ischaemia-reperfusion (I/R) model. 2. Seventy-nine female Wistar albino rats were divided into eight groups. The first three groups underwent sham operation; group 1 was the control group, group 2 received L-arginine and group 3 received L-NAME. Ischaemia was produced in the remaining five groups by ligation of the superior mesenteric artery for 30 min followed by 60 min reperfusion. Group 4 rats were control I/R rats and groups 5-8 received either L-arginine, L-NAME, D-arginine or D-NAME, respectively. 3. Both luminol and lucigenin CL was significantly increased in I/R groups compared with sham-operated groups. L-Arginine significantly reduced CL measurements. D-Arginine was also protective, but not as much as L-arginine. Both L - and D-arginine had in vitro O₂^?-scavenging potential, as tested by the xanthine-xanthine oxidase system. N^G-Nitro-L-arginine methyl ester decreased lipid peroxidation values in addition to reducing CL measurements. Nitric oxide concentrations were significantly increased in I/R groups in comparison with sham-operated groups. Peroxynitrite formation was increased by I/R. Treatment with L-NAME was beneficial by reducing NO concentrations in the reperfused ileum. 4. In our I/R model, O₂^?, NO and other ROS were increased. Although NOS inhibitors were effective in reducing oxidative damage, increasing NO concentrations with L-arginine was also beneficial, presumably due to the ability of L-arginine to inhibit phagocyte adherence and its radical scavenging potential. In fact, NO may have different effects in terms of tissue injury or protection depending on the concentration of oxygen and the haemodynamic state of the tissue.     

雌激素的血管作用:快速作用,新的机制和治疗潜力

Although estrogen-dependent effects on thevasculature were first observed more than a centuryago, many of the mechanisms by which estrogensinteract with the vascular wall have been identified onlyin the past 15 years. Estrogens bind to vascularestrogen receptors (ER), including the ERα, the novelERβ as well as to membrane-bound receptors.