• 약학회지
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• 제43권3호
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• pp.397-403
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• 1999

The present study examined the effect of a methanol extract of Evodiae Fructus on the cardiovascular function in N-nitro-L-arginine methyl ester (NAME)-induced hypertensive Wistar rats after treatment over 6 weeks. In rats treated with NAME, blood pressure, weight of heart, aorta media thickness and media/lumen ratio significantly (p<0.05) increased, whereas coronary flow and heart rate of isolated heart significantly (p<0.05) decreased compared with control group at 6 weeks. In rats treated with NAME and Evodiae Fructus, blood pressure, aorta media/lumen ratio significantly(p<0.05) decreased compared with NAME treated group at 6 weeks. These results suggest that Evodiae Fructus is applicable to the treatment of hypertension and vascular hypertrophy.

• The Korean Journal of Pain
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• 제19권2호
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• pp.142-145
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• 2006

Background: Nitric oxide (NO) is involved in the transmission and modulation of nociceptive information at the peripheral, spinal cord and supraspinal levels. We conducted this experiment to assess the antinociceptive effects of a nonselective nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the modulation of pain in rats subjected to the formalin test. Methods: Formalin 5% was injected in the right hind paw after intraperitoneal (IP) injection of various doses of L-NAME (0.5 mg/kg, 1.5 mg/kg with and without L-arginine 100 mg/kg, 5.0 mg/kg). The number of flinches was measured. Results: Formalin injected into the rat hind paw induced a biphasic nociceptive behavior. IP injected L-NAME diminished the nociceptive behaviors in a dose-dependent manner during phases 1 and 2. The concomitant injection of L-arginine reversed the antinocipetive effect of L-NAME. Conclusions: The data demonstrates that a nonselective NOS inhibitor, L-NAME, possesses antinociceptive properties in rats subjected to the formalin test, and the antinociceptive effect of L-NAME is reversed by the concomitant administration of L-arginine.

• Journal of Korean Neurosurgical Society
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• 제38권4호
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

• The Korean Journal of Physiology and Pharmacology
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• 제10권4호
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• pp.213-216
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• 2006

The present study was aimed to determine whether nitric oxide (NO) plays a role in the regulation of aquaporin (AQP) channels in the kidney. Male Brattleboro rats ($250{\sim}300\;g$ body weight) were used. The experimental group was treated with $N^G$-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 1 week, and cotreated with indomethacin (5 mg/kg, twice a day, i.p.) for the last two days. Control groups were treated with either L-NAME for 1 week, indomethacin for 2 days, or without any drug treatment. The abundance of AQP1, AQP2 and AQP3 proteins in the kidney was determined by Western blot analysis. Indomethacin downregulated AQP channels, whereas L-NAME by itself showed no significant effects on them. The indomethacin-induced downregulation of AQP2 and AQP3 was significantly blunted in L-NAME-treated rats, while that of AQP1 was not affected. These results suggest that endogenous NO, when stimulated, may downregulate AQP channels that are specifically regulated by AVP/cAMP pathway in the kidney.

• The Korean Journal of Physiology
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• 제28권2호
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• pp.225-231
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• 1994

The present study was undertaken to investigate the role of endogenous nitric oxide in renin release under different physiological conditions. In the first series of experiments, renin release was either inhibited by acute volume-expansion (VE) or stimulated by clipping one renal artery in the rat. VE was induced by intravenous infusion of saline (0.9% NaCl) up to 5% of the body weight over 45 min under thiopental (50 mg/kg, IP) anesthesia. VE caused a decrease of plasma renin concentration (PRC). With $N^G-nitro-L-arginine$ methyl ester $(L-NAME,\;5\;{\mu}g/kg\;per\;min)$ superadded to VE, PRC decreased further. The magnitude of increase in plasma atrial natriuretic peptide levels following VE was not affected by the L-NAME. In two-kidney, one clip rats, L-NAME-supplementation resulted in a decrease, and L-arginine-supplementation an increase of PRC. Plasma atrial natriuretic peptide levels were significantly lower in the L-arginine group than in the control. Blood pressure did not differ among the L-NAME, L-arginine, and control groups. In another series of experiments, the renin response to a blockade of NO synthesis was examined using in vitro preparations from isolated renal cortex. L-NAME significantly increased basal renin release, although it was without effect on the isoproterenol-stimulated release. These findings suggest that endogenous nitric oxide significantly contributes to the renin release. Since many factors may affect the renin release in vivo, an interaction between NO and renin under various pathophysiological states is to be further defined.

• 치위생과학회지
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• 제15권6호
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• pp.800-806
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• 2015

이 연구는 triptolide와 L-NAME의 측두하악관절 통증조절효과를 확인하기 위하여 포르말린으로 유도된 측두하악관절 통증모델에서 triptolide와 L-NAME의 소뇌연수조 내 각각의 얄물의 단독 투여에 따른 통증행위반응과 두 약물의 병용 투여에 따른 상호작용이 통증행위반응에 미치는 영향을 평가하여 다음과 같은 결과를 얻었다. 먼저, 관절강 내로 주입한 5% 포르말린($30{\mu}l$)은 유의한 통증행위반응을 유발하였고, 2차 통증행위반응 관찰 시 포르말린 주입 전 $1{\mu}g/10{\mu}l$ triptolide 투여군($163.33{\pm}29.11$회)은 포르말린군($308{\pm}33.04$회)과 비교 시 통증행위반응이 유의하게 감소하였다. $0.1{\mu}g/10{\mu}l$의 L-NAME 투여군의 1, 2차 통증행위반응의 결과, 각각 $5.80{\pm}3.75$회, $92.30{\pm}16.04$회로 포르말린 주입군 $25.4{\pm}6.59$회, $285.60{\pm}29.93$회와 비교 시 유의하게 감소되었다. 다음으로, $1{\mu}g/10{\mu}l$의 triptolide와 $0.01{\mu}g/10{\mu}l$의 L-NAME 병용 투여군에서 1, 2차 통증행위반응이 $0.80{\pm}0.80$회, $96.50{\pm}26.16$회로 나타나 $22.50{\pm}19.15$회, $163.33{\pm}29.11$회로 나타난 $1{\mu}g/10{\mu}l$ trtiptolide군과 비교 시 유의하게 통증행위반응이 경감되었다. 이러한 연구결과는 측두하악관절 통증조절의 예방 및 치료에 있어 활용가능한 천연물로 triptolide가 제시될 수 있으며, 천연물과 화합물들의 병용 투여를 통해 그 효과를 증가시킬 수 있을 것으로 기대된다.

• Journal of Yeungnam Medical Science
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• 제14권2호
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• pp.337-349
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• 1997

세균 내독소에 의하여 발생하는 패혈성 쇼크와 혈관 반응성 감소의 원인을 관찰하였다. 혈관 절편이 고정된 실험조에 세균 내독소 0.2 mg 투여한 경우 $36{\pm}3.65$ nM NO가 발생되었고, NO 발생에 의한 혈관 이완 효과를 억제하기 위해 전처치한 L-MAME, methylene blue는 혈관 절편의 phenylephrine (PE) 유발 수축 반응을 증가시켰으며 methylene blue에 의해 더 강한 수축 반응의 증가가 관찰되었다. 이때 혈관 내피세포가 존재할 경우에 PE에 대한 혈관 반응성이 증가되는 경향을 나타내었다. 세균 내독소 투여에 의해 acetylcholine 유발 혈관 이완은 증가되는 경향을 나타내었고, 전처치한 L-NAME, methylene blue에 의해 혈관 절편의 acetylcholine (ACh) 유발 이완은 억제되었으며 methylene blue에 의해 현저히 억제되었다. 그러나 세균 내독소를 투여하지 않은 군의 ACh 유발 혈관 이완 반응은 methylene blue에 의해서만 억제되었다. 결론적으로 세균 내독소에 의한 혈관 반응성 감소와 혈관 이완 반응은 NO가 발생되어 guanylyl cyclase를 활성화하여 유발된다고 생각되며, 세균 내독소에 의한 효과는 L-arginine NO pathway 보다는 cyclic GMP 신호전달계를 경유한 경로에서 더 많은 영향을 받는것으로 사료된다.

• Journal of Applied Biological Chemistry
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• 제62권3호
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• pp.265-273
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• 2019

This study aimed to evaluate the anti-atherosclerotic and anti-hypertensive effects of six different plant extracts using a N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced rat model of hypertension. All extracts were administered orally for six weeks. At the end of the study period blood pressure, blood flow, aortic histopathology, and hepatic endothelial nitric oxide synthase (eNOS) expression were measured. Subsequently, we also measured the levels of intracellular reactive oxygen species, nitric oxide (NO), and anti-inflammatory cytokines in vitro. Based on these screening results, we selected extracts of Cinnamomum cassia (C. cassia) and Salvia miltiorrhiza (S. miltiorrhiza) for further evaluation. C. cassia and S. miltiorrhiza extracts ameliorated hypertension and atherosclerosis in L-NAME-treated rats in a dose-dependent manner. In addition, a mixture of C. cassia and S. miltiorrhiza had an additive effect to reduce blood pressure, increase blood flow, and normalize aortic tissue. This mixture demonstrated anti-oxidative and anti-inflammatory activities in vitro. In conclusion, although further analysis of the therapeutic mechanism is required, the anti-hypertensive and anti-atherosclerotic effects of this mixture are likely mediated by increased eNOS expression, and its anti-oxidative and anti-inflammatory activities.

• 대한수의학회지
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• 제45권4호
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• pp.485-493
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• 2005

We studied the effects of trazodone on arterial blood pressure in anesthesized guinea pigs, and on vascular responses in isolated thoracic aorta. Trazodone produced a concentration-dependent relaxation in phenylephrine-precontracted endothelium intact (+E) rings, but not in a KCl-precontracted aortic rings. These relaxant effects of trazodone on +E rings were significantly greater than those on denuded (-E) rings. The trazodone-induced relaxation was suppressed by glibenclamide and tetrabutylammonium, but not by N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), methylene blue (MB), nifedipine, indomethacin, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC) and clotrimazole. In vivo, infusion of trazodone elicited a significant decrease in arterial blood pressure. Trazodone-induced blood pressure lowering was markedly inhibited by intravenous pretreatment of prazosin but not by pretreatment of saponin, L-NNA, L-NAME, MB, nifedipine, glibenclamide, clotrimazole and NCDC. In addition, trazodone produced an increase in twitch force of isolated papillary muscle and left ventricular pressure of perfused heart. These findings suggest that the endothelium-independent vasorelaxant effect of trazodone may be explained by activation of $Ca^{2+}$-activated and ATP-sensitive $K^+$ channels, and the hypotensive effect of trazodone is not associated with cardiac contraction.

• 대한수의학회지
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• 제41권3호
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• pp.299-304
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• 2001

토끼 적출 신동맥에 있어서 acetylcholin(Ach)에 의한 이완작용에 대한 nitric oxide(NO) 합성 억제제인 $N^{G}$-nitro-L-arginine methyl ester(L-NAME)과 prostanoid 합성 억제제인 indomethacin의 영향을 관찰하였다. Ach($10^{-8}-3{\times}10^{-5}M$)에 대한 이완작용은 내피세포를 제거시킴으로서 완전히 사라졌다. L-NAME ($10^{-4}M$)은 Ach ($10^{-8}-3{\times}10^{-5}M$)의 이완작용을 현저히 감소시켰으며 L-arginine ($10^{-3}M$)에 의해 Ach의 이완작용에 대한 L-NAME ($10^{-4}M$)의 억제효과가 현저히 약하게 나타났다. Indomethacin ($10^{-6}M$)은 Ach ($10^{-8}-3{\times}10^{-5}M$)의 이완작용에 영향을 미치지 못하였다. L-NAME ($10^{-4}M$)에 indomethacin ($10^{-6}M$)의 첨가는 Ach ($10^{-8}-3{\times}10^{-5}M$)의 이완작용이 L-NAME ($10^{-4}M$) 단독의 경우보다 더 큰 억제효과를 나타내었다. 이와 같은 결과로 토끼적출 신동맥에서 Ach은 내피세포 의존성 이완작용을 나타내며, NO와 prostanoid가 수반되어 나타나는 것으로 사료되어진다.