Effect of simvastatin on endothelium-dependent vaso-relaxation and endogenous nitric oxide synthase inhibitor

AIM: To investigate the effect of simvastatin on endothelium-dependent vasorelaxation and endogenous nitric oxide synthesis inhibitor asymmetric dimethylarginine (ADMA) in rats and cultured ECV304 cells. METHODS: Endothe-lial injury was induced by a single injection of low density lipoprotein (LDL) (4 mg/kg, 48 h) in rats or incubation with LDL (300 mg/L) or oxidative-modified LDL (100 mg/L) in cultured ECV304 cells, and vasodilator responses to acetylcholine (ACh) in the aortic rings and the level of ADMA, nitrite/nitrate (NO) and tumor necrosis factor-alpha (TNF-α) in the serum or cultured medium were determined. And the adhesion of the monocytes to endothe-lial cells and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in the cultured ECV304 cells were measured. RESULTS: A single injection of LDL decreased endothelium-dependent relaxation to ACh, markedly increased the serum level of endogenous ADMA and TNF-α, and reduced serum level of NO. Pretreatment with simvastatin (30 or 60 mg/kg) markedly attenuated inhibition of vasodilator responses to ACh, the increased level of TNF-α and the decreased level of NO by LDL, but no effect on serum concentration of endogenous ADMA. In cultured ECV304 cells, LDL or ox-LDL markedly increased the level of ADMA and TNF-α and potentiated the adhesion of monocytes to endothelial cells, concomitantly with a significantly decrease in the activity of DDAH and serum level of NO. Pretreatment with simvastatin (0.1, 0.5, or 2.5 μmol/L) markedly decreased the level of TNF-α and the adhesion of monocytes to endothelial cells, but did not affect the concentration of endogenous ADMA and the activity of DDAH. CONCLUSION: Simvastatin protect the vascular endothelium against the damages induced by LDL or ox-LDL in rats or cultured ECV304 cells, and the beneficial effects of simvastatin may be related to the reduction of inflammatory cytokine TNF-α level.     

川芎嗪对麻醉犬心血管作用的初步观察

Tetramethylpyrazine (TMPZ) has been shown to be one of the active principles of the Chinese medicinal plant "Chuan Qong", Ligusticum Wallichii Franch.TMPZ (4, 8 or 16 mg/kg) given intravenously to anesthetized dogs transiently decreased the blood pressure and markedly increased the heart rate and maximal rate of the left ventricular pressure. These cardiovascular effects of TMPZ seemed to be dosedependent. Prior administration of propranolol (2 mg/kg, I. V.) abolished the effect of TMPZ on the heart, leaving the depressor effect of TMPZ unchanged. Reserpinization of the dog affected the cardiovascular actions of TMPZ in a way similar to propranolol. The cardiovascular responses to TMPZ still persisted after cervical vagotomy. The injection of TMPZ at a dose of 0.4～2 mg/kg into the vertebral artery induced no significant hemodynamic response.These results indicate that in the anesthetized dog TMPZ exhibited positive inotropic and chronotropic effects on the heart mediated by sympatho-adrenergic mechanism. In addition, TMPZ seemed to have some direct dilating action on the peripheral bloodvessels.     

Modification of aspirin and ethanol-induced mucosal damage in rats by intragastric application of resiniferatoxin

The capsaicin analogue ‘resiniferatoxin’ (RTX) was used to investigate the role of capsaicin-sensitive sensory nerves in gastric mucosal injury caused by intragastric (ig) acidified aspirin (200 mg/kg in 2 ml of 0.15 N HCl) or ethanol (2 ml of 50% v/v or 96%) in pylorus-ligated rats. Animals were sacrificed 1, 2 and 4 h later, when gastric secretory responses, number and severity of mucosal lesions were calculated. Intragastric RTX (0.6–1.8 μg/kg) prevented mucosal injury in a dose-dependent manner induced by topical acidified aspirin. The protective effect lasted for 1h and was accompanied by inhibition of gastric acid secretion by RTX. RTX (0.6 and 1.0 μg/kg) co-administered with ethanol reduced mucosal injury caused by 50% ethanol; the protective effect of RTX being more apparent when the drug was given 15 min prior to 50% ethanol. Unexpectedly, RTX co-administered with absolute ethanol aggravated the ethanol-induced mucosal damage. It is concluded that capsaicin-sensitive sensory nerves mediated microcirculatory changes in gastroprotection and these involve inhibition of gastric acid secretion.     

Increase of insulin sensitivity in diabetic rats received Die—Huang—Wan,a herbal mixture used in Chinese traditional medicine

AIM：Effects on insulin sensitivity of Die-Huang-Wan,the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine,were investigated in vivo.METHODS:The obese Zucker rats were employed as insulin-resistant animal model.Also,insulin-resistance was induced by the repeatedintraperitoneal injections of long-acting human insulin at 0.5U/kg three times daily into adult male Wistar rats.Insulin resistance was identified using the loss of tolbutamide(10mg/kg) or electroacupuncture(EA)-induced plasma glucose lowering action.The plasma glucose concentration was examined by glucose oxidase assay.RESULTS:The plasma glucose-lowering action induced by tolbutamide was significantly enhanced in obese Zucker rats receiving the repeated administration of Die-Huang-Wan at dosage of 26mg/kg for 3d.Furthermore,administration of Die-Huang-Wan delayed the formation of insulin resistance in rats that were induced by the daily repeated injection of human long-acting insulin at 0.5U/kg three times daily and identified by the loss of tolbutamide-or EA-induced hypoglycemia.In streptozotocininduced diabetic rats,oral administration of metformain at 320mg/kg once daily made an increase of the response to exogenous short-acting human insulin 15d later.This is consistent with the view that metformin can increase insulin sensitivity.Similar treatment sith Die-Huang-Wan at an effective dose(26.0mg/kg) also increased the plasma glucose lowering action of exogenous insulin at 10d later.The effect of Die-Huang-Wang on insulin sensitivity seems to produce more rapidly than that of metformin.CONCLUSION;The present study found that oral administration of Die-Huang-Wan increased insulin sensitivity and delayed the development of insulin resistance in rats.     

Individual differences in responses to nicotine： tracking changes from adolescence to adulthood

Aim： The present study determined the extent to which individual differences in responses to the psychostimulating effect of nicotine during adolescence predict similar individual differences during adulthood in rats. We also examined the possible long-term effects of adolescent nicotine exposure on adult prepulse inhibition （PPI） of the acoustic startle response, a measure of sensorimotor gating ability. Methods： During the adolescent phase, rats were administered saline, 0.10, 0.40, or 0.60 mg/kg nicotine via subcutaneous injections for 8 days, and motor activity was measured daily. During the adult phase, these rats were treated with the same nicotine dose as in adolescence for 8 additional days. The adolescent saline rats （now adults） were subdivided into four groups and administered saline, 0.10, 0.40, or 0.60 mg/kg nicotine, respectively. PPI was assessed 12 days after the last nicotine treatment. Results： During both phases, nicotine increased motor activity across test days in a dose-dependent manner. Motor activity of rats treated with nicotine during adolescence was positively correlated with the activity recorded from the same rats during adulthood. In both phases, there were profound individual differences in the responses to the nicotine treatments. In addition, adolescent rats treated with nicotine did not show decreased motor response to the initial exposure to nicotine. Finally, adolescent exposure to nicotine at 0.4 mg/kg, but not adulthood exposure to the same dose of nicotine, produced a robust disruption of PPI, with individual rats showing different degrees of PPI disruption. Conclusion： These findings suggest that adolescent rats have increased sensitivity to the psychostimulating effect and decreased sensitivity to the aversive effect of nicotine. Also, nicotine exposure during adolescence may have long-term detrimental effects on sensorimotor gating ability.     

Validation of a simple automated movement detection system for formalin test in rats

Aim: To investigate the validity and sensitivity of an automatic movement detection system developed by our laboratory for the formalin test in rats. Methods:The effects of systemic morphine and local anesthetic lidocaine on the nociceptive behaviors induced by formalin subcutaneously injected into the hindpaw were examined by using an automated movement detection system and manual measuring methods. Results: Formalin subcutaneously injected into the hindpaw produced typical biphasic nociceptive behaviors (agitation). The mean agitation event rate during a 60-min observation period increased linearly following increases in the formalin concentration (0.0%, 0.5%, 1.5%, 2.5%, and 5%, 50 μL). Systemic application of morphine of different doses (1, 2, and 5 mg/kg) 10-min prior to formalin injection depressed the agitation responses induced by formalin injection in a dose-dependent manner, and the antinociceptive effect induced by the largest dose (5 mg/kg) of morphine was significantly antagonized by systemic application of the opioid receptor antagonist naloxone (1.25 mg/kg). Local anesthetic lidocaine (20 mg/kg) injected into the ipsilateral ankle subskin 5-min prior to formalin completely blocked the agitation response to formalin injection. These results were comparable to those obtained from manual measure of the incidence of flinching or the duration time of licking/biting of the injected paw. Conclusion: These data suggest that this automated movement detection system for formalin test is a simple, validated measure with good pharmacological sensitivity suitable for discovering novel analgesics or investigating central pain mechanisms.     

Effect of pravastatin on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine in rat aorta

Aim: To investigate the effects of pravastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine (LPC), the major component of oxidized low-density lipoprotein, in rat thoracic aorta. Methods: Both the endothelium-dependent relaxation response to acetylcholine and the endotheliumindependent relaxation response to sodium nitroprusside of aortic rings were measured by recording isometric tension after the rings were exposed to LPC in the absence or presence of pravastatin to estimate the injury effect of LPC and the protective effect of pravastatin on the aortic endothelium, respectively. Results: Exposure of aortic rings to LPC (1-10μmol/L) for 30 min induced a significant concentration-dependent inhibition of endothelium-dependent relaxation to acetylcholine, but did not affect endothelium-independent relaxation in response to sodium nitroprusside. Pre-incubation of aortic rings with pravastatin (0.3-3mmol/L) for 15 min and then co-incubation of the rings with LPC (3 μmol/L) for another 30 min significantly attenuated the inhibition of endothelium-dependent relaxation induced by LPC. This protective effect of pravastatin (1 mmol/L) was abolished by N^G-nitro-L-arginine methyl ester (30 μmol/L), an inhibitor of nitric oxide synthase, but not by indomethacin (10 μmol/L), an inhibitor of cyclooxygenase. Moreover, protein kinase C inhibitor chelerythrine (1μmol/L) the superoxide anion scavenger superoxide dismutase (200 kU/L), and the nitric oxide precursor L-arginine (3 mmol/L) also improved the impaired endotheliumdependent relaxation induced by LPC, similar to the effects of pravastatin.C onclusion: Pravastatin can protect the endothelium against functional injury induced by LPC in rat aorta, a fact which is related to increasing nitric oxide bioavailability.     

A new buprenorphine analogy, thenorphine, inhibits morphine-induced behavioral sensitization in mice

AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the loco-motor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-adminis     

The protective effect of cuminaldehyde on gastric mucosa in Rattus norregicus of experimental gastric ulcer北大核心CSCD

Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E2(PGE2) and NO in gastric tissue also significantly increased. The content of malondialdehyde (MDA) decreased. Compared with the model group, cuminaldehyde decreased the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat serum, and decreased the activity of myeloperoxidase (MPO). Conclusions Cuminaldehyde has good antioxidant stress ability and anti-inflammatory activity, increases the expression of protective factors, enhances the defense ability of gastric mucosa, and has obvious protective effect on acute gastric ulcer in R. norregicus. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Taurine protects against low-density lipoprotein-induced endothelial dysfunction by the DDAH/ADMA pathway

Asymmetric dimethylarginine (ADMA), a major endogenous nitric oxide (NO) synthase inhibitor, is thought to be a key contributor for endothelial dysfunction. Decrease in activity of dimethylarginine dimethylaminohydrolase (DDAH), a major hydrolase of ADMA, causes accumulation of ADMA in some risk factors of atherosclerosis, including hypercholesterolemia. Taurine is a semi-essential amino acid that has previously been shown to have endothelial protective effects. The present study was to test whether the protective effect of taurine on endothelial function is related to modulation of the DDAH/ADMA pathway. A single injection of native LDL (4 mg/kg, i.v.) markedly reduced endothelium-dependent vasorelaxation and the plasma level of NO, and increased plasma concentrations of ADMA, malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-alpha). Treatment with taurine in vivo (60 or 180 mg/kg) significantly attenuated the inhibition of endothelium-dependent vasorelaxation and the reduced level of NO, and decreased the elevated levels of ADMA, MDA, and TNF-alpha. Incubation human umbilical vein endothelial cells (HUVECs) with ox-LDL (100 microg/ml) for 24 h markedly increased the medium levels of lactate dehydrogenase (LDH), ADMA, TNF-alpha and MDA, and decreased the level of NO in the medium and the intracellular activity of DDAH. Taurine (1 or 5 microg/ml) significantly attenuated the increases in the levels of LDH, ADMA, TNF-alpha and MDA, and the decrease in the level of NO and the activity of DDAH induced by ox-LDL in HUVECs. The present results suggested that taurine protected against endothelial dysfunction induced by native LDL in vivo or by ox-LDL in endothelial cells, and the protective effect of taurine on the endothelium is related to decrease in ADMA level by increasing of DDAH activity.     

Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level

1. Oxide low-density lipoprotein (ox-LDL) is believed to play an important role in early events of atherogenesis, and asymmetric dimethylarginine (ADMA) is associated with the development of endothelial dysfunction. The present study examined the effect of a single injection of native low-density lipoprotein (LDL) on endothelium function and the serum level of ADMA and the effect of probucol on endothelium function and ADMA level in rats. 2. Endothelial injury was induced by intravenous injection of LDL at the dose of 2, 4, or 6 mg kg(-1) for 24, 48, or 72 h, and vasodilator responses to acetylcholine in the aortic rings and serum levels of ADMA, nitrite/nitrate (NO) and malondialdehyde (MDA) were determined. 3. Pretreatment with LDL markedly reduced endothelium-dependent relaxation in a concentration-dependent manner. Inhibition of vasodilator responses to acetylcholine by LDL was abolished in the presence of L-arginine (3 x 10(-4) M). Serum levels of ADMA and MDA were significantly elevated in the rats pretreated with LDL, while serum level of nitrite/nitrate was markedly decreased. 4. Pretreatment with probucol significantly improved endothelium-dependent relaxation, decreased concentrations of ADMA and MDA and increased nitrite/nitrate level in the rats treated with LDL. A similar effect was seen in the rats pretreated with an antioxidant vitamin E. 5. These results suggest that a single injection of native LDL causes endothelial dysfunction by elevation of ADMA levels and that the protective effect of probucol on endothelial cells is related to reduction of ADMA concentration.     

Protective effects of daviditin A against endothelial damage induced by lysophosphatidylcholine

Previous investigations have indicated that endogenous inhibitors of nitric oxide synthase (NOS) such as asymmetric dimethylarginine (ADMA) may play an important role in endothelium dysfunction, and some antioxidant drugs improve endothelium function via reduction of ADMA level. The present study examined the antioxidation and endothelial protection of daviditin A, a xanthone compound. Daviditin A significantly inhibited Cu(2+)-induced low-density lipoprotein (LDL) oxidation (EC50: 38.7 microM) and scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC50: 57.5 microM). Vasodilator responses to acetylcholine in rings of the isolated thoracic aorta were impaired in the presence of lysophosphatidylcholine (LPC)(5 mg/l). Daviditin A (10 or 30 microM) significantly attenuated inhibition by LPC of endothelium-dependent relaxation. Incubation of ECV304 cells with LPC (5 mg/l) for 24 h markedly elevated lactate dehydrogenase (LDH) activity and the levels of malondialdehyde (MDA) and ADMA, and decreased the content of nitric oxide (NO) and the activity of dimethylarginine dimethylaminohydrolase (DDAH). Daviditin A (1, 3 or 10 microM) significantly attenuated the increased release of LDH, increased content of MDA, and decreased level of NO induced by LPC. Daviditin A (3 or 10 microM) significantly inhibited the increased concentration of ADMA. Daviditin A (10 microM) significantly attenuated the decreased activity of DDAH. The present results suggest that daviditin A preserves endothelial dysfunction elicited by LPC, and the protective effect of daviditin A on the endothelium is related to reduction of ADMA concentration.     

Effect of fenofibrate on LDL-induced endothelial dysfunction in rats

Previous investigations have demonstrated that asymmetric dimethylarginine (ADMA) is an important factor contributing to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in hyperlipidaemic patients. In the present study in rats treated with native low-density lipoprotein (nLDL), we addressed the question of whether the beneficial effect of fenofibrate on endothelial cells is related to reduction of the ADMA concentration. A single injection of nLDL (4 mg/kg, 48 h) markedly reduced endothelium-dependent relaxation in response to acetylcholine and the plasma level of nitrite/nitrate and increased the plasma concentrations of ADMA, malonyldialdehyde (MDA) and tumour necrosis factor- (TNF-). Treatment with fenofibrate (30 or 100 mg/kg) significantly reduced the inhibition of vasodilator responses to acetylcholine, decreased the elevated levels of ADMA, MDA and TNF-, and enhanced the decreased level of nitrite/nitrate in the rats treated with LDL. These results suggest that the protective effect of fenofibrate on endothelial cells in rats treated with LDL may be related to the reduction of ADMA concentration.     

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.     

Sex difference in the effect of aspirin on rat platelet aggregation and arachidonic acid metabolism

The rat platelet aggregation induced by collagen was stronger in males than in females. The platelet malondialdehyde (MDA) production was more in males than in females, and the platelet cyclooxygenase activity was higher in males than in females. Aspirin at a dose of 10 mg/kg inhibited the collagen-induced aggregation in males, but not in females. Aspirin at a dose of 5 mg/kg blocked the MDA production only in males, but aspirin at a dose of 10 mg/kg inhibited the MDA production in both sexes. The effect of aspirin on the cyclooxygenase activity was only in males, but aspirin at a dose of 10 mg/kg inhibited the MDA production in both sexes. The effect of aspirin on the cyclooxygenase activity was similar to that on the MDA production. In gonadectomized rats, the MDA production and the cyclooxygenase activity were decreased by castration, and they were increased by ovariectomy. Aspirin at a dose of 5 mg/kg failed to inhibit them in castrated rats. Besides, in in vitro experiments, aspirin also inhibited the MDA production and the aggregation. Nevertheless, there was no sex difference in the content of arachidonic acid, a substrate of platelet cyclooxygenase. It is suggested that there is a sex difference in rat platelet cyclooxygenase activity, and it is closely related to the sex difference in the antiplatelet effect of aspirin.     

左旋精氨酸对氧自由基损害兔胸主动脉内皮的保护作用(英文)

用离体兔胸主动脉淋浴式灌注方法探讨左旋精氨酸对内、外源性OFR损伤血管内皮功能的保护作用,结果:用二乙二硫氨基甲酸盐(DETC)产生的内源性OFR与电解缓冲液产生的外源性OFR均可明显抑制血管内皮依赖性扩张,并使血管壁MDA含量增加,左旋精氨酸能对抗内、外源性OFR所致MDA增加与内皮依赖舒血管功能损害。     

一氧化氮中介雷米普利拉对氧自由基损伤兔胸主动脉内皮的保护作用

采用离体兔胸主动脉淋浴灌注方法，探讨雷米普利拉（Ｒａｍ）对氧自由基损伤血管内皮功能的保护作用及其机理．结果发现，电解Ｋｒｅｂｓ液产生的氧自由基明显抑制血管内皮依赖性舒张，降低血管壁氧化氮（ＮＯ）和ｃＧＭＰ含量，并使丙二醛含量增加；Ｒａｍ消除电解所致的上述作用，并呈现剂量依赖性；ＮＯ合成的前体物质─—Ｌ－精氨酸亦具有相似的保护作用；Ｒａｍ和Ｌ－精氨酸的保护作用均可被ＮＯ合成酶抑制剂所阻断。这些结果提示，Ｒａｍ抗氧自由基损伤血管内皮的作用可能与其促进内皮细胞合成，释放ＮＯ有关。Ｐ＜０．０１，ｃｏｍｐａｒｅｄｗｉｔｈｃｏｎｔｒｏｌ．Ｐ＜０．０５，Ｐ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＥｌｅ；Ｐ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＲａｍΔΔＰ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＬ－Ａｒｇ．ＳｉｍｉｌａｒｒｅｓｕｌｔｗａｓｏｂｔａｉｎｅｄｉｎｔｈｅｔｉｓｓｕｅｔｒｅａｔｅｄｗｉｔｈＬ－Ａｒｇ．Ｈｏｗｅｖｅｒ．ｔｈｅｅｆｆｅｃｔｏｆＲａｎｉｏｒＬＡｒｇｗａｓａｂｒｏｇａｔｃｄｉｎｔｈｅｐｒｅｓｅｎｃｅｏｆＮＡｒｇ．Ｒｅｄｕｃｔｉｏｎｂｙｅｌｅｃｔｒｏｌｙｓｉｓｏｆｎｉｔｒｉｔｅｖａｌｕｅｗａｓｎｏｔｉｎｆｌｕｅｎｃｅｄ?