Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study examined the acute toxicity and antinociceptive effects of diphenyl diselenide (PhSe)2, given orally (p.o.), in chemical and thermical models of pain in mice. Diphenyl diselenide (7.8-312 mg/kg, p.o.) did not cause mortality. This compound did not change plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels in mice after 72 h of exposure. Diphenyl diselenide (1-100 mg/kg, p.o.) inhibited acetic acid-, capsaicin-, glutamate-, bradykinin(BK)- and phorbol myristate acetate (PMA)-induced pain. Diphenyl diselenide also reduced glutamate-, bradykinin-, PMA-induced paw oedema formation. Moreover, diphenyl diselenide caused a significant increase in tail-immersion response latency time. Diphenyl diselenide co-injected subplantarly in association with glutamate-induced a significant reduction of the licking and in the paw oedema formation induced by glutamate. The local pre-treatment of mice with l-arginine, intraplantarly, restored antinociception caused by diphenyl diselenide or N(G)-nitro-L-arginine methyl ester (L-NAME) when analyzed against glutamate-induced nociception. The pre-treatment of mice with dithiothreitol (DTT) intraplantarly restored local antinociception caused by diphenyl diselenide or 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) when analyzed against glutamate-induced nociception. These results indicate that diphenyl diselenide produced antinociception in several models of pain through mechanisms that involve an interaction with not only nitrergic system but also via interaction with redox modulatory sites of glutamate receptors.
 ...
PMID:Antinociceptive properties of diphenyl diselenide: evidences for the mechanism of action. 1712 7

The role of nitric oxide (NO) in acute renal failure (ARF) is debatable. In the present study, we investigated the effect of acute administration of NO donor, Sodium nitroprusside (SNP), L-Arginine (L-Arg) and NO synthase inhibitor, N(omega)-L-arginine methyl ester (L-NAME) in Fe-NTA induced renal toxicity. Rats were pretreated with SNP (2.5 mg/kg i.p), L-Arg (125 mg/kg, i.p.) and L-NAME (10 mg/kg, i.p.) prior to administration of Fe-NTA (8 mg iron/kg body weight, i.p.) to determine the urea and creatinine levels along with biochemical analysis of oxidative stress. Fe-NTA administration markedly increased the BUN and serum creatinine level which was coupled with a marked lipid peroxidation, decreased levels of reduced glutathione and total nitric oxide levels of rat kidneys coupled with significant morphological alterations. It also resulted in the significant increase in tumor necrosis factor-alpha (TNF-alpha) in serum. Concomitant treatment with SNP and L-Arg significantly reduced the serum creatinine and BUN levels, reduced lipid peroxidation in a significant manner, restored levels of reduced glutathione, increased total nitric oxide levels and restored the normal morphology. Pretreatment with SNP and L-Arg attenuated the levels of TNF-alpha in serum in a significant manner. Prior administration of L-NAME reversed the protective effects produced by SNP and L-Arg. Present findings strongly suggest that nitric oxide plays a significant role in the pathophysiology of iron-induced renal failure and administration of NO donors can be valuable in the treatment of ARF.
 ...
PMID:Sodium nitroprusside and L-arginine attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats. 1728 Jul 60

This study examined the role of cytochrome P450 (CYP) metabolites of arachidonic acid (AA) to rat corporal smooth muscle tone. 11, 12-Epoxyeicosatrienoic acid (EET) (10(-11)-10(-6 )M) produced dose-dependent relaxation of rat (control; 10 weeks old) corpus cavernosum with a pD(2) value of 8.8+/-0.2 and a maximal relaxation of 80+/-9%, whereas 20-hydroxyeicosatetraenoic (20-HETE) did not have an effect. EET-mediated relaxation of corpus cavernosum was attenuated by 71+/-3%, 55+/-2%, 53+/-5% and 84+/-3% in the presence of nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an inhibitor of nitric oxide (NO) synthase, iberiotoxin (5 x 10(-8) M), an inhibitor of calcium-activated potassium (BK) channels, glibenclamide (10(-5) M), an inhibitor of ATP-sensitive K(+) channels or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10(-5) M), an inhibitor of soluble guanylyl cyclase, respectively. EET-mediated relaxation of rat corpus cavernosum was significantly less in the streptozotocin (STZ)-treated (diabetic) and 30 weeks old (older) animals compared to control. Carbachol (10(-9)-10(-4) M)-induced relaxation was significantly reduced whereas phenylephrine (PE) (10(-9)-5 x 10(-3) M)-induced contraction was significantly increased in the cavernosum strips from old and diabetic rats compared to the control. Pre-incubation of the cavernosum strips obtained from control, older or diabetic rats with N-hydroxy-N'-(4-butyl-2-methyl-phenyl)-formamidine (HET0016), a selective inhibitor of 20-HETE synthesis, or 1-cyclohexyl-3-dodecyl urea (CDU), a specific inhibitor of soluble epoxide hydrolase (sEH) resulted in a significant attenuation of PE-induced contraction and improvement in carbachol-induced relaxation. We conclude that 11, 12-EET-induced relaxation of the rat corpus cavernosum involves activation of cGMP/NO pathway as well as activation of ATP-sensitive K(+) channels and BK channels. These results also suggest that inhibition of 20-HETE production or reduction of EET inactivation may have therapeutic potential to prevent erectile dysfunction associated with diabetes and aging.
 ...
PMID:Role of cytochrome P450 metabolites of arachidonic acid in regulation of corporal smooth muscle tone in diabetic and older rats. 1785 73

The present study investigated the cardiovascular effects of orexin (OX)-A and OX-B in the nucleus tractus solitarii (NTS) and delineated the engagement of nitric oxide (NO) and GABA in OX-induced cardiovascular responses. In adult male Sprague-Dawley rats maintained under propofol anesthesia, microinjection bilaterally into the NTS of OX-A or OX-B evoked bi-directional cardiovascular effects in a dose-dependent manner. At a lower dose (5 pmol), OX-A or OX-B decreased systemic arterial pressure (SAP), heart rate (HR), and power density of the vasomotor components of SAP signals, our experimental index for sympathetic neurogenic vasomotor tone. At higher doses (>20 pmol), these two compounds elicited cardiovascular excitatory responses. These bi-directional cardiovascular effects of OX were abolished by co-injection of an OX(1) receptor antagonist, 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl-urea hydrochloride (SB-334867, 0.75 nmol) or the OX(2) receptor antiserum (1:20). In addition, the vasodepressor effects of low dose (5 pmol) OX-A or OX-B in the NTS were attenuated by a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 5 nmol), a neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (2.5 pmol) or the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (250 pmol). The vasopressor effects of high dose (200 pmol) OX were reversed by co-administration with GABA(A) or GABA(B) receptor antagonist, bicuculline methiodine (10 pmol) or 2-hydroxy saclofen (100 pmol), or l-NAME (5 nmol). Our results indicate that OX-A or OX-B elicited bi-directional cardiovascular effects via OX receptor-dependent mechanisms. The vasodepressor effects of OX were induced by the nNOS-derived NO and activation of sGC-associated signaling pathway, whereas the vasopressor effects were mediated by interaction with GABAergic or nitrergic neurotransmission in the NTS.
 ...
PMID:Nitric oxide and GABA mediate bi-directional cardiovascular effects of orexin in the nucleus tractus solitarii of rats. 1791 8

To explore detrimental effects of advanced oxidation protein products-bovine serum albumin (BSA) on endothelial function and compare the favorable effects of angiotensin-converting enzyme (ACE) inhibitors: captopril and enalapril. Male Sprague-Dawley rats were randomly divided into groups: control, advanced oxidation protein products-BSA, captopril (10, 20 mg/kg/day), enalapril (15 mg/kg/day), and N(G)-nitro-l-arginine methyl ester (l-NAME, 300 mg/kg/day) plus captopril (20 mg/kg/day) groups. All animals were given advanced oxidation protein products-BSA (100 mg/kg/day, i.v.) except for control group (iv. equal volume of PBS). Rats in other groups were received different drugs intragastrically after advanced oxidation protein products-BSA administration. Endothelium-dependent relaxation of thoracic aorta was assayed. Content of nitrite/nitrate (NO), malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and of ACE in Sera, as well as renal function index including blood urea nitrogen and creatinine were measured. After 30 days, the endothelium-dependent relaxation of blood vessels in received advanced oxidation protein products-BSA rats was significantly impaired compared with control rats. The impairment was accompanied by decreases of serum NO, activity of GSH-Px and SOD. Administration of captopril and enalapril not only decreased damage of endothelium-dependent relaxation, but also reverse the changes of MDA levels, NO content and activity of SOD. The protective effect of captopril was abolished by L-NAME. Blood urea nitrogen and creatinine had no significant differences between various groups. ACE activities were decreased in high captopril and enalapril groups, but did not significantly change in other groups. The results suggested that captopril and enalapril have similar effects on endothelial dysfunction induced by advanced oxidation protein products-BSA, which indicated that protective effects of captopril are not related to sulfhydryl group.
 ...
PMID:Protective effects of ACE inhibitors on vascular endothelial dysfunction induced by exogenous advanced oxidation protein products in rats. 1833 54

Nitric oxide (NO) is important for the homeostasis of organ functions. We studied the structural and functional changes in the cardiovascular (CV) and renal systems following early NO deprivation by various nonspecific and specific NO synthase (NOS) inhibitors: N-nitro-L-arginine methyl ester (L-NAME), N-nitro-L-arginine (L-NA), S-methyl-isothiourea (SMT), and L-N6-(1-iminoethyl)-lysine (L-Nil). The aim is to elucidate the involvement of NO through endothelial or inducible NOS (eNOS and iNOS). Drugs were given to spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY) from a young age (5-wk-old). Physiological, biochemical, and pathological examinations were performed. L-NAME and L-NA treatment caused a rapid increase in tail cuff pressure (TCP). The TCP of SHR reached a malignant level within 30 days with signs of stroke, proteinuria [corrected] severe glomerular sclerosis, and moderate ventricular hypertrophy (VH). The plasma nitrite/nitrate was reduced, while creatinine, urea nitrogen and uric acid were elevated. The renal tissue cyclic guanosine monophosphate (cGMP) was decreased with an elevated collagen content. The numbers of sclerotic glomeruli, arteriolar and glomerular injury scores were markedly increased, accompanied by reduction in renal blood flow, filtration rate, and fraction. Plasma endothelin-1 was increased following L,-NAME or L-NA treatment for 10 days. The expression of eNOS and iNOS mRNA was depressed by L-NAME and L-NA. The relevant iNOS inhibitors, SMT and L-Nil depressed the iNOS expression, but did not produce significant changes in CV and renal systems. The continuous release of NO via the eNOS system provides a compensatory mechanism to prevent the genetically hypertensive rats from rapid progression to malignant phase. Removal of this compensation results in VH, stroke, glomerular damage, renal function impairment, and sudden death.
 ...
PMID:Malignant alterations following early blockade of nitric oxide synthase in hypertensive rats. 1844 11

The activity of arginase converting arginine into ornithine and urea is of particular interest among many factors regulating NO production in the cells. It is known that by competing with NO-synthase for common substrate, arginase can affect the NO synthesis. In the present work, the properties of arginase from the frog Rana temporaria L. urinary bladder epithelial cells possessing the NO-synthase activity were characterized, and possible contribution of arginase to regulation of NO production by epithelial cells was studied. It has been shown that the enzyme had the temperature optimum in the range of 55-60 degrees C, K(m) for arginine 23 mM, and V(max) about 10 nmol urea/mg protein/min, and its activity was effictively inhibited by (S)-(2-boronoethyl)-L-cysteine (BEC), an inhibitor of arginase, at concentrations from 10(-6) to 10(-4) M. The comparison of arginase activity in various frog tissues revealed the following pattern: liver > kidney >> brain > urinary bladder (epithelium) > heart > testis. The arginase activity in the isolated urinary bladder epithelial cells was 3 times higher than that in the intact urinary bladder. To evaluate the role of arginase in the regulation of NO production, epithelial cells were cultivated in the media L-15 or 199 containing different amounts of arginine; the concentration of NO2-, the stable NO metabolite, was determined in the culture fluid after 18-20 h of cells incubation. The vast majority of the produced nitrites are associated with the NOS activity, as L-NAME, the NOS-inhibitor, decreased their accumulation by 77.1% in the L-15 medium and by 80% in 199 medium. BEC (10(-4) M) increased the nitrite production by 18.0 % +/- 2.7 in the L-15 medium and by 24.2 +/- 3.5 in the 199 medium (p < 0.05). The obtained data indicate a relatively high arginase activity in the frog urinary bladder epithelium and its involvement in regulation of NO production by epithelial cells.
 ...
PMID:[Arginase activity in the frog urinary bladder epithelial cells and its involvement in regulation of nitric oxide production]. 1872 9

We investigated the involvement of matrix metalloproteinases (MMPs), tissue inhibitor (TIMP) and endothelin-1 (ET-1) in the renal damage in spontaneously hypertensive rats (SHR) following nitric oxide (NO) deprivation. SHR received Nomega-nitro-L-arginine methyl ester (L-NAME) from 5 wk-old for a period of 30 days. An ETA antagonist, FR139317 was used. We gave SHR FR139317 alone and cotreatment with L-NAME. L-NAME caused systemic hypertension, decrease in plasma nitrate/nitrite, increases in blood urea nitrogen and creatinine, impairment of glomerular dynamics. NO deprivation reduced the renal tissue cGMP, but it increased the collagen volume fraction, number of sclerotic glomeruli, arteriolar injury score and glomerular injury score. In addition, L-NAME elevated the plasma ET-1 at day 5. Cotreatment with FR139317 alleviated the L-NAME-induced functional and structural changes of renal glomeruli. L-NAME administration for 5 to 10 days resulted in decreases in MMP2 and MMP9 with increasing TIMP2. After L-NAME for 15 days, opposite changes (increases in MMP2 and MMP9 with a decrease in TIMP2) were observed. FR139317 cotreatment ameliorated the L-NAME-induced changes in MMP2 and MMP9 throughout the 30-day observation period. The ETA antagonist cotreatment attenuated the L-NAME-induced increase in TIMP2 before day 15, but not after day 20. The results indicate that ET-1, MMPs and TIMP are involved at the early stage (before 10 days) of glomerular sclerosis and arteriosclerosis with functional impairment following NO deprivation. The changes in MMPs and TIMP at the late stage (after 20 days) may be a compensatory response to prevent further renal damage.
 ...
PMID:Endothelin and gelatinases in renal changes following blockade of nitric oxide synthase in hypertensive rats. 1893 14

This study was undertaken to examine the possible role of the DNA-binding activity of nuclear factor-kappa B (NF-kappaB) in rat of radiocontrast-media-induced nephropathy (RCIN) and to explore the characteristic of RCIN in rats and the role of NF-kappaB in its occurrence. Forty-eight adult male Sprague-Dawley (SD) rats were randomly divided into Groups A-D. Rats of Groups A and B were intravenously injected with NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) and indomethacin (10 mg/kg), respectively. Rats of Groups C and D were intravenously injected with 1-M phosphate buffer (PH = 8.4 3 mL/kg) and normal saline (NS 2 mL/kg), respectively. After 30 min, Groups A and D were injected with NS (8 mL/kg) and Groups B and C were injected with diatrizoate (DTZ 8 mL/kg). After injected contrast media (CM) for 6 h, the serum creatinine and blood urea nitrogen of rat in Group B increased sharply as compared with Groups A, C, and D. After 48 h, the data recovered to 49.28 +/- 8.81 mumol/L and 6.72 +/- 2.75 mmol/L, respectively. Vacuolization of the tubule epithelial cells of the kidney was observed in Group A. Especially, these pathological changes were most obvious in outer medulla. Contrast to group A, the DNA-binding activity of NF-kappaB in rat kidney of Group B reached a peak at the 6th h and recovered to the normal level after the 48th h. CM mainly damages renal tubular-interstitial, which appears the earliest and most serious in the outer medulla. Activation of NF-kappaB of renal may be one of the mechanisms of RCIN occurrence.
 ...
PMID:The role of nuclear factor-kappaB in rats of radiocontrast-media-induced nephropathy. 1911 Oct 3

Arginine takes part in many metabolic cell processes. It is not only involved in the dynamic cycle of interconversion with prolin and glutamine but also serves as a precursor for protein, nitric oxide, creatine, polyamines, agmatine and urea synthesis. Particularities of arginase and NO-synthase pathways of L-arginine conversion under the X-ray radiation in the leucocytes-radiosensitive cells of peripheral blood, under the per os administration of L-arginine and L-NAME (NG-nitro-L-arginine methyl ester) to rats were detected. It was shown that both L-arginine (arginase and NO-synthase main substrate) and L-NAME (nonspecific inhibitor of NO-synthase) had a positive correct influence on the organism in case of decreasing of NO overproduction under the X-ray radiation.
 ...
PMID:[Particularities of arginase and NO-synthase pathways of L-arginine metabolism in leucocytes of peripheral blood of rats in conditions of chronic x-ray irradiation]. 1987 76


<< Previous 1 2 3 4 5 6 7 8 Next >>