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Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro

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Asian Journal of Andrology 2008年第2期10卷 307-312页

作者： Jun Chen Ji-Hong Liu Tao Wang Heng-Jun Xiao Chun-Ping Yirl Jun Yang Department of Urology Tongji Hospital Huazhong University of Science and Technology Wuhan 430030 China Department of Urology The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630 China Department of Pharmacy Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Aim： To further investigate the relaxation mechanism of neferine （NED, a bis-benzylisoquinoline alkaloid extracted （isolated） from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro. Methods： The effects of Nef on the concentrations of cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP） in isolated and incubated rabbit corpus cavernosum tissue were recorded using ^125I radioimmunoassay. Results： The basal concentration of cAMP in corpus cavernosum tissue was 5.67 ± 0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner （P 〈 0.05）, but this effect was not inhibited by an adenylate cyclase inhibitor （cis-N-[2-phenylcyclopentyl]azacyclotridec-1-en-2-amine, MDL-12, 330A）（P 〉 0.05）. The accumulation of cAMP induced by prostaglandin Et （PGEt, a stimulator of cAMP production） was also augmented by Nef in a dose-dependent manner （P 〈 0.05）. The basal concentration of cGMP in corpus cavernosum tissue is 0.44 ± 0.09 pmol/mg. Nef did not affect this concentration of cGMP, either in the presence or in the absence of a guanyl cyclase inhibitor （1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ）（P 〉 0.05）. Also, sodium nitroprusside （SNP, a stimulator of cGMP production）-induced cGMP production was not enhanced by Nef （P 〉 0.05）. Conclusion： Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity. （Asian JAndro12008 Mar; 10： 307-312）

关键词： neferine cyclic adenosine monophosphate cyclic guanosine monophosphate rabbit corpus cavernosum

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Studies on Relationship between Serum Nitric Oxide and Plasma cyclic guanosine monophosphate and Prolonged Bleeding after Medical Abortion as well as Prophylaxis and Treatment of Bleeding with Traditional Chinese Medicine

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Journal of Reproduction and Contraception 1999年第4期10卷 220-226页

作者：廖玎玲谭布珍辛华贺晓菊

Objectives To study the relationship between serum nitric oxide (NO and plasma cyclic guanosine monophosphate (cGMP) and prolonged bleeding after medical abortion. Methods A total of 120 women having received medical abortions at random were recruited and divided into two groups: the one (Group A,n=60) taking 'Gong Fu Mixture(Uterus Recovering Mixture)' and the other (Group B,n=60) not taking it after abortion. On d 10, 20 and 30 after medical abortion, serum NO and plasma cGMP were tested before and after mifepristone administration and 10 d later by Gresis reaction method and radioimmunoassay respectively. Results NO concentration in serum and cGMP concentration in plasma decreased significantly after taking mifepristone given (P<0.05). Ten days later, the number of those with bleeding discontinuation in the group A was significantly greater than that in the group B (P<0.05). Serum NO level and plasma cGMP level in the group A decreased more significantly than those in the group B (P<0.05). Conclusion The slow decrease of serum NO and plasma cGMP is closely related to prolonged bleeding after medical abortion. “Gong Fu Mixture (uterus recovering mixture)” is effective in prevention and treatment of prolonged bleeding.

关键词： Mifepristone Induced abortion Nitric Oxide Uterine hemorrhage cyclic guanosine monophosphate

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Nitric oxide promotes survival of cerebellar granule neurons cultured in vitro through the Akt pathway

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Neural Regeneration Research 2011年第20期6卷 1559-1563页

作者： Lin Wang Mei Li Lihua Zhou Department of Anatomy Zhongshan School of Medicine Sun Yat-sen University Guangzhou 510080 Guangdong Province China Department of Neurology Second Affiliated Hospital Sun Yat-sen University Guangzhou 510080 Guangdong Province China

In this study, cerebellar granule neurons were used to examine the role of nitric oxide on cell survival. The N-methyI-D-aspartic acid receptor antagonist, MK-801, and the soluble guanylate cyclase antagonist, 1H-[1, 2, 4]oxadiazolo-[4, 3-a] quinoxalin-1 -one, decreased cell viability, induced caspase-3, and decreased phosphorylated-Akt levels, suggesting that blockade of nitric oxide production promotes apoptosis of differentiating cerebellar granule neurons. After administration of sodium nitroprusside, an endogenous nitric oxide donor, cell viability recovered, caspase-3 expression was decreased, and phosphorylated-Akt levels increased. This study provides direct evidence that nitric oxide can sustain the survival of developing cerebellar granule neurons in vitro through the nitric oxide-Akt pathway. Moreover, endogenous nitric oxide exerts these effects in a cyclic guanosine monophosphate-dependent manner while exogenous nitric oxide does so in a cyclic guanosine monophosphate-independent manner.

关键词： nitric oxide cerebellar granule neurons development apoptosis Akt cyclic guanosine monophosphate neural regeneration

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Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction

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Asian Journal of Andrology 2018年第5期20卷 448-453页

作者： Guo-Tao Chen Bai-Bing Yang Jian-Huai Chen Zheng Zhang Lei-Lei Zhu He-Song Jiang Wen Yu Yun Chen Yu-Tian Dai Department of Andrology Nanjing Drum Tower Hospital Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China.

Erectile dysfunction （ED） associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase （PK） has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate （cGMP） levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.

关键词： cyclic guanosine monophosphate endothelial nitric oxide synthase erectile dysfunction intracavernous pressure pancreatic kininogenase type 2 diabetes

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Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

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Asian Pacific Journal of Tropical Biomedicine 2023年第7期13卷 287-295页

作者： Yucinda YY Khor Siew-Keah Lee Dharmani Devi M Wei Chih Ling Department of Pre-clinical Sciences M.Kandiah Faculty of Medicine and Health SciencesUniversiti Tunku Abdul RahmanSelangorMalaysia Department of Pharmacology Faculty of MedicineUniversiti MalayaKuala LumpurMalaysia

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 *** endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of *** vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also ***,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was ***:The systolic blood pressure was significantly decreased in SHR treated with *** impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR *** also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in ***:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)*** increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

关键词： Epigallocatechin-3-gallate Vascular protection Antihypertension Tetrahydrobiopterin cyclic guanosine monophosphate Angiotensin typeⅠreceptor Spontaneously hypertensive rats

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Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

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Neural Regeneration Research 2013年第8期8卷 693-701页

作者： Kwang Taek Kim Kyung Jin Chung Han Sae Lee Il Gyu Ko Chang Ju Kim Yong Gil Na Khae Hawn Kim Department of Urology Gachon University Gil Medical CenterGachon University Department of Physiology College of MedicineKyung Hee University Department of Urology Chungnam National University HospitalChungnam National University School of Medicine

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

关键词： neural regeneration brain injury cerebral ischemia Tadalafil phosphodiesterase type-5 inhibitor dopamine dopamine D2 receptor cyclic guanosine monophosphate grants-supported paper photographs-containing paper neuroregneration

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Beneficial Effect of Berberis amurensis Rupr. on Penile Erection

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Chinese Journal of Integrative Medicine 2018年第6期24卷 448-454页

作者： Rui Tan Yun Jung Lee Kyung Woo Cho Dae Gill Kang Ho Sub Lee College of Oriental Medicine and Professional Graduate School of Oriental Medicine Wonkwang University Hanbang CardioRenal Syndrome Research Center Wonkwang University Brain Korea 21 Plus Team Professional Graduate School of Oriental MedicineWonkwang University

Objective： To investigate whether the methanol extract of Berberis amurensis Rupr. （BAR） augments penile erection using in vitro and in vivo experiments. Methods： The ex vivo study used corpus cavemosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure （ICP）, blood pressure, mean arterial pressure （MAP）, and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats. Results： Preconstricted with phenylephrine （PE） in isolated endothelium- intact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester （L-NAME）, a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-l-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME 1H-[1,2,4]- oxadiazole-[4,3-α ]-quinoxalin-l-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium （TEA, P〈0.01）, a nonselective K＋ channel blocker, 4-aminopyridine （4-AP, P〈0.01）, a voltage-dependent K＋ channel blocker, and charybdotoxin （P〈0.01）, a large and intermediate conductance Ca2. sensitive-K＋ channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently. Conclusion： BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2. sensitive-K＋（BK＋ and IK＋） channels in the corpus cavemosum.

关键词： penile erection Berberis amurensis Rupr. nitric oxide cyclic guanosine monophosphate K+ channel

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Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through thecGMP/cGMP-dependent protein kinase pathway

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World Journal of Gastroenterology 2008年第35期14卷 5461-5466页

作者： Chun-Yu Cai Zheng-Xu Cai Xin-Yi Gu Lu-Juan Shan Yong-Xiao Wang Xue-Zhe Yin Qing-Hui Qi Hui-Shu Guo Department of Internal Medicine the Affiliated Hospital of Yanbian University Yanji 133000 Jilin Province China Department of Neurology the First Affiliated Hospital of Dalian Medical University Dalian 116011 Liaoning Province China Centralab Zhongshan Affiliated Hospital of Dalian University Dalian 116001 Liaoning Province China Centralab the First Affiliated Hospital of Dalian Medical University Dalian 116011 Liaoning Province China Center for Cardiovascular Sciences Albany Medical College Albany NY 12208 United States

AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.

关键词： Dendroaspis natriuretic peptide cyclic guanosine monophosphate Protein kinase G Proteinkinase A Gastric motility

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Role of nitric oxide during early phase myocardial ischemic preconditioning in rats

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Chinese Medical Journal 2008年第13期121卷 1210-1214页

作者： HAN Hong-guang WANG Zeng-wei ZHANG Nan-bin ZHU Hong-yu Department of Cardiovascular Surgery Xijing Hospital of Fourth Military Medical University Xi'an Shaanxi 710032 China Department of Cardiovascular Surgery General Hospital of Shenyang Military Command Shenyang Liaoning 110016 China

Background To date, there have been no reports on altered nitric oxide （NO） content in ischemia/reperfusion with regard to in vivo preconditioning procedures. These studies are important for understanding the mechanisms of NO during early myocardial ischemic preconditioning. The aim of the present study was to investigate the mechanisms of NO during early myocardial ischemic preconditioning by measuring levels of NO and cyclic guanosine monophosphate （cGMP）, as well as activity of nitric oxide synthase （NOS） in ischemia/reperfusion with respect to preconditioning in rats. Methods Sixty-six female Sprague-Dawley rats were randomly divided into four groups： ischemic preconditioning group （IP）, ischemia/reperfusion group （I/R）, control group （CON）, and preconditioning procedure group （PC）. In the PC group, rats were further divided into PC1-, PC1＋, PC2-, PC2＋, PC3-, and PC3＋ subgroups. Rats underwent left coronary artery occlusion and reperfusion, and subsequently, NOS activity and levels were assessed with spectrophotometric analysis. cGMP contents were measured with radioimmunoassay. Results The level of NO and cGMP, as well as the activity of NOS, were significantly higher in the IP group compared to the I/R and CON groups （P 〈0.05）. During preconditioning prior to prolonged ischemia, NO and cGMP levels varied markedly with ischemia and reperfusion. The levels of NO repeatedly increased when the heart was exposed to three episodes of 5-minute ischemia, and were almost completely reversed during each reperfusion period. NO and cGMP levels were significantly different between the 5-minute period of ischemia and the same period of reperfusion during preconditioning. Conclusions NO plays an important role during early phase myocardial ischemic preconditioning in rats. NO and cGMP could be triggers and mediators of early phase myocardial ischemic preconditioning. Altered NOS activity following ischemic stress could be the primary inducer of higher NO levels detecte

关键词： ischemic preconditioning nitric oxide nitric oxide synthase cyclic guanosine monophosphate rats

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Low expression of vascular endothelial growth factor and high serum level of cyclic guanine monophosphate as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rat

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Chinese Journal of Traumatology 2020年第2期23卷 107-112页

作者： I Ketut Suyasa Anak Agung Wiradewi Lestari Department of Orthopedic and Traumatology Faculty of MedicineUdayana UniversityBaliIndonesia Department of Clinical Pathology Faculty of MedicineUdayana UniversityBaliIndonesia

Purpose:Severe damage to the femoral head in patients with osteonecrosis has a high impact on *** early diagnosis,the treatment outcome is still *** study aimed to explore the expression of vascular endothelial growth factor(VEGF)and cyclic guanine monophosphate(cGMP)serum level as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar ***:This was an exper imental study using randomized post-test only control group design,with samples using 10-14 weeks Wistar male *** were then divided into 6 groups:3 groups without intervention,and 3 groups with intervention using 40%alcohol given *** one group from intervention and control group was euthanized by the end of the week for 3 consecutive *** femurs were examined under microscope for osteonecrosis,immunohistochemically for VEGF,and blood serum for cGMP ***:VEGF expression in the femoral head of alcohol-exposed Wistar rats was lower than those not exposed to alcohol(p<0.005).Blood serum cGMP levels of alcohol-exposed Wistar rats were higher than those not exposed to alcohol(p<0.005).The number of necrotic osteocytes in the femoral head of Wistar rats exposed to alcohol was greater than those not exposed to alcohol(p<0.005).There are significant differences between VEGF,cGMP levels,and number of necrotic osteocytes in the control group and treatment at 1st,2nd'and 3rd week(p<0.005).Conclusions:Based on the result of this study,VEGF and cGMP may be considered as diagnostic bio-markers for alcohol-induced femoral head osteonecrosis.

关键词： cyclic guanosine monophosphate Osteonecrosis Vascular endothelial growth factor

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