No abstract available.
Humans ; Nitric Oxide* ; Tissue Donors*

PURPOSE: To investigate the effect of mitomycin C on the proliferation of cultured trabecular cells and its relation to nitric oxide (NO) production. METHODS: The effect of NO donor, SIN-1, on the proliferation of primarily cultured porcine trabecular meshwork cells was studied with MTT assay. After treatment with mitomycin C at various concentrations for 1 hour, the proliferation was assessed by MTT assay and the production of nitrite was assessed by Griess reaction after 24 hours and 3 days respectively. RESULTS: SIN-1 significantly inhibited proliferation of cultured trabecular meshwork cells (p<0.05). Mitomycin C also suppressed the cellular proliferation(p<0.05) but did not affect the production of nitrite (p>0.05). CONCLUSIONS: Both NO donor and mitomycin C have an inhibitory effect on the proliferation of trabecular meshwork cells. However, inhibitory effect of mitomycin C was not related to the production of NO.
Humans ; Mitomycin* ; Nitric Oxide* ; Tissue Donors ; Trabecular Meshwork*

PURPOSE: To investigate whether the effect of benzalkonium chloride (BAK) on the proliferation of human Tenon capsule fibroblasts (HTCF) is mediated by nitric oxide (NO) in tissue culture . METHODS: HTCF were exposed to various concentrations of BAK for 24 hr and the cellular proliferation and production of NO were assessed by MTT and Griess assays, respectively. A non-specific nitric oxide synthase inhibitor, 0, 5 mM N(omega)-Nitro-L-arginine methyl ester (L-NAME), or NO donor, 100 micro M sodium nitroprusside (SNP), was co-administered with BAK to assess the effect of NO on the proliferation of cells. RESULTS: BAK decreased cellular proliferation in a dose-dependent manner and this effect was accompanied with decreased nitrite production. The cellular proliferation was increased significantly with BAK/SNP co-administration but decreased with BAK/L-NAME co-administration. CONCLUSIONS: NO donor increased the proliferation of HTCF which was decreased by BAK. The effect of BAK on the proliferation of HTCF may be possibly mediated by NO.
Benzalkonium Compounds* ; Cell Proliferation ; Fibroblasts* ; Humans* ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Nitric Oxide* ; Nitroprusside ; Tenon Capsule* ; Tissue Donors

Nitric oxide (NO) is emerging as a potential anti-cancer agent to overcome tumor cell resistance to conventional therapeutic agents. NO is a short-life molecule produced from L-arginine by the nitric oxide synthase (NOS). There are three isoforms of the enzyme: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). Each of these isoforms may be expressed in a variety of cell types. The actions of NO are highly variable in oncology revealing both sides of the spectrum as an anti-neoplastic versus a pro-neoplastic agent. The final activity of NO is dependent on its working microenvironment, including the type of cell exposed to NO, the redox state of the reaction, as well as the final intracellular concentration and the duration of exposure to NO. NO donors mimic continuous production of NO in a wide range of time intervals (seconds to days). Thus, multiple biological and (pro- versus anti-) neoplastic responses are elicited from NO donors depending on the half-life and the type of cell exposed to the compound. This paper is a review of the current knowledge of various roles of NO in cancer.
Arginine ; Half-Life ; Humans ; Hydrazines ; Neurons ; Nitric Oxide ; Nitric Oxide Synthase ; Oxidation-Reduction ; Protein Isoforms ; Tissue Donors

Nitric oxide has been implicated in many physiologic processes that influence both acute and long-term control of kidney function. Its net effect in the kidney is to promote natriuresis and diuresis, contributing to adaptation to variations of dietary salt intake and maintenance of normal blood pressure. A pretreatment with nitric oxide donors or L-arginine may prevent the ischemic acute renal injury. In chronic kidney diseases, the systolic blood pressure is correlated with the plasma level of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. A reduced production and biological action of nitric oxide is associated with an elevation of arterial pressure, and conversely, an exaggerated activity may represent a compensatory mechanism to mitigate the hypertension.
Acute Kidney Injury ; Arginine ; Arterial Pressure ; Blood Pressure ; Diuresis ; Hypertension ; Kidney ; Natriuresis ; Nitric Oxide ; Nitric Oxide Donors ; Nitric Oxide Synthase ; Plasma ; Renal Insufficiency, Chronic

OBJECTIVE: Nitric oxide(NO) is implicated in a wide range of biological processes in tumors and is produced in glioma. To investigate the role of NO and its interaction with the tumoricidal effects of anticancer drugs, we study the antitumor activities of NO donors, with or without anticancer drugs, in human glioma cell lines. METHODS: U87MG and U373MG cells were treated with the NO donors sodium nitroprusside(SNP) and S-nitroso-N-acetylpenicillamine(SNAP), alone or in combination with the anticancer drugs 1, 3-bis(2-chloroethyl)-1-nitrosourea(BCNU) and cisplatin. Cell viability, cell proliferation, DNA fragmentation, nitrite level, and the expression of Bcl-2 and Bax were determined. RESULTS: NO was markedly increased after treatment with SNP or SNAP; however, the addition of the anticancer drugs did not significantly affect NO production. NO donors or anticancer drugs reduced glioma cell viability and, in combination, acted synergistically to further decrease cell viability in a dose- and time-dependent manner. Cell proliferation was inhibited and apoptosis were enhanced by combined treatment. Bax expression was increased by combined treatment, whereas Bcl-2 expression was reduced. The antitumor cytotoxicity of NO donors and anticancer drugs differed according to cell type. CONCLUSION: BCNU or cisplatin can inhibit cell viability and proliferation of glioma cells and can induce apoptosis. These effects are further enhanced by the addition of a NO donor which modulates the antitumor cytotoxicity of chemotherapy depending on cell type. Further biological, chemical, and toxicological studies of NO are required to clarify its mechanism of action in glioma.
Apoptosis ; Biological Processes ; Carmustine ; Cell Line ; Cell Proliferation ; Cell Survival ; Cisplatin ; DNA Fragmentation ; Drug Therapy ; Glioma* ; Humans ; Nitric Oxide Donors* ; Nitric Oxide* ; Sodium ; Tissue Donors

Nitric oxide (NO) is known to mediate penile erection by activating intracellular cyclic GMP pathway. It is also suggested that cGMP pathway, on penile erection, has dominant role over the other secondary messenger pathway with cAMP, etc. Based on the hyposthesis that activation of NO-cGMP pathway could represent a more physiologic and effective approach in the treatment of erectile dysfunction, several NO donors and activator of cGMP have been used in human and animal studies of impotence. However the efficacy of those remains debatable. In the present study, we investigated the effect of NO donor [linsidomine chlorhydrate (SIN-1), S-nitroso-N-acetylpcnicillamine (SNAP), sodium nitroprusside (SNP)] alone and in combination with zaprinast (cGMP specific phosphodiesterase inhibitor) on penile erection in rats. NO donors used in this study, except SNP, did not induce penile erection sufficiently. SNP-induced penile erection is comparable to the erection induced by cavernosal nerve stimulation. However, direct applicaion of SNP in the treatment of impotence may not be acceptable as it causes a marked hypotension. Zaprinast given intracayernously either alone or in combination with NO donor may not be clinically effective. Combination with zaprinast is not shown to enhance the effect of NO donor on penile erection. Therefore, combination of NO donor with other drugs modulating different pathway may be a therapeutic approach to erectile dysfunction worthy of further investigation.
Animals ; Cyclic GMP ; Erectile Dysfunction ; Humans ; Hypotension ; Male ; Nitric Oxide* ; Nitroprusside ; Penile Erection* ; Rats* ; Tissue Donors*

PURPOSE: To investigate the effect of nitric oxide (NO) on the contraction of cultured human trabecular meshwork cells (HTMCs). METHODS: After embedding them into collagen gels, primarily cultured HTMCs were exposed to NO donors, such as sodium nitroprusside (SNP) or S-Nitroso-N-acetylpenicillamine (SNAP), for 1 week at various concentrations, and the contraction of the collagen gels was measured. Cellular survival and NO production were measured with MTT assay and Griess assay, respectively. RESULTS: Though SNP and SNAP did not significantly affect cellular survival, they markedly enhanced NO production. Both sodium nitroprusside and SNAP inhibited the contraction of collagen gels by about 10% in dose and time-dependent manners (p<0.05). CONCLUSIONS: NO donors inhibited the contraction of collagen gels in vitro. Thus, NO donors may relax trabecular meshwork and enhance trabecular outflow.
Collagen* ; Gels* ; Humans ; Nitric Oxide* ; Nitroprusside ; S-Nitroso-N-Acetylpenicillamine ; Tissue Donors ; Trabecular Meshwork*

PURPOSE: To investigate the effect of triamcinolone acetonide (TA) on the survival, nitric oxide (NO) production, and migration of cultured human trabecular meshwork (TM) cells. METHODS: After exposure to TA, indomethacin, and dexamethasone for 2 days, the survival and nitrite production of the primarily cultured human TM cells were assessed with MTT and Griess assays respectively. The effect of co-exposure to the NO donor, sodium nitroprusside, was also assessed. A migration assay was done to evaluate the effect of TA on the activity of TM cells. RESULTS: Cellular survival increased after exposure to TA at low concentration but decreased at high concentration. TA decreased the production of NO significantly (p<0.05). Exposure to indomethacin and dexamethasone revealed similar results. TA reversibly inhibited the migration of TM cells. CONCLUSIONS: TA decreases the production of NO and inhibits the migration of TM cells. TA at high concentration decreases cellular survival accompanied with decreased NO production. These effects of TA on TM cells may result in the elevation of intraocular pressure.
Dexamethasone ; Humans ; Indomethacin ; Intraocular Pressure ; Nitric Oxide ; Nitroprusside ; Tissue Donors ; Trabecular Meshwork* ; Triamcinolone Acetonide* ; Triamcinolone*

PURPOSE: Vaginal engorgement depends, in part, on the relaxation of vaginal smooth muscle. The aim of this study was to evaluate the role of nitric oxide(NO) in the relaxation of the vaginal smooth muscle. MATERIALS AND METHODS: New Zealand White female rabbits(n=8) were sacrificed and distal 1/3 of the vagina was dissected. Strips of vaginal tissues were immediately processed for isometric tension measurement in the organ bath. The vaginal strips were precontracted with phenylephrine and the responses to electrical field stimulation(EFS) or sodium nitroprusside were examined. Each preparations was also processed immunohistochemically to determine the presence of neuronal NO synthase(n-NOS) in the tissue. RESULTS: EFS caused a frequency-dependent relaxation, which was significantly inhibited in the presence of Nw-nitro-L-arginine methyl ester(L-NAME), a competitive inhibitor of NOS. Sodium nitroprusside, a NO donor, caused concentration-dependent relaxations in the vaginal tissue and the relaxation was not affected by L-NAME(10-4M). n-NOS immunoreactivity was detected in perivascular space and vicinity of vaginal smooth muscle. CONCLUSIONS: These results suggest that the relaxation of the rabbit vaginal smooth muscle is partly mediated by the NO pathway.
Baths ; Female ; Humans ; Muscle, Smooth* ; Neurons ; New Zealand ; Nitric Oxide* ; Nitroprusside ; Phenylephrine ; Relaxation* ; Tissue Donors ; Vagina