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Query: UNIPROT:P30536 (
PBS
)
9,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
1. Diabetes mellitus type I was induced in 3-month old male C57 BL/KS-mdb mice (N = 24) by ip injection of streptozotocin (STZ, 45 mg/kg body weight) for 5 days. 2. To determine the possible protective effects of nitric oxide inhibition against hyperglycemia, the STZ-diabetic rats received two doses of NG-nitro-L-arginine- methyl ester (L-
NAME
) (10 mg/kg body weight and 10 mg/mouse) dissolved in
PBS
for 45 consecutive days. Another group of STZ-treated rats was similarly treated with L-arginine (5 mg/mouse). 3. Blood glucose levels were 118 +/- 37 mg/dl after 8 days of L-
NAME
administration (10 mg/kg body weight, N = 12) and 186 +/- 22 mg/dl (N = 12) after 5 days of L-
NAME
administration at the 5 mg/mouse dose. Treatment with L-arginine (5 mg/mouse, N = 12) caused a significant increase in blood glucose level to 151 +/- 17.5 mg/dl, showing the relevance of nitric oxide formation in this type of diabetes. 4. In STZ-diabetic mice treated with L-
NAME
(N = 12), diuresis was reduced by approximately 58% compared to STZ animals, whereas in L-arginine-treated animals (N = 12) diuresis returned to STZ levels. Urinary protein excretion, which was significantly affected by STZ (123% compared to control) was significantly reduced by 66% after treatment with L-
NAME
for 45 days, whereas treatment with L-arginine caused a return to STZ values. 5. Urinary kallikrein excretion, which was reduced by 80% in STZ mice compared to control, returned to control levels after L-
NAME
treatment. 6. The present results suggest a relationship between nitric oxide levels and the reduction of diabetic state and improved renal function by L-
NAME
.
...
PMID:Streptozotocin-induced hyperglycemia is decreased by nitric oxide inhibition. 774 93
1. The role of endogenous bradykinin in mean arterial blood pressure (BP) homeostasis was studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats by the use of a bradykinin B2-receptor antagonist (BKant; Hoe 140, 11.6 micrograms kg-1) and converting enzyme (kininase II) inhibitor (captopril, 10 mg). To obtain a response to captopril that was induced through inhibition of kinin-degradation only and not through inhibition of angiotensin II-formation, the studies were performed on binephrectomized male rats to eliminate the renin-angiotensin system. 2. The role of the nitric oxide (NO) and the adrenergic systems were evaluated by the use of NO-synthase inhibitor (L-
NAME
, 0.3 g kg-1) and phentolamine (2 mg kg-1), respectively. 3. The rats were anaesthetized and pretreated with two injections of vehicle (
PBS
) or drugs spaced 5 min apart:
PBS
+
PBS
; BKant +
PBS
;
PBS
+ L-
NAME
; BKant + L-
NAME
; or phentolamine + L-
NAME
. All rats were given captopril 15 min later. Time-control groups were treated with L-
NAME
but not captopril. 4. In WKY rats, captopril did not significantly alter BP in any of the groups. In the SHR-
PBS
+
PBS
group, on the other hand, captopril induced an immediate fall in BP (delta BP = -23 +/- 4 mmHg, P < 0.0017) which was completely blocked by BKant (delta BP = 2 +/- 2 mmHg) (P < 0.0011). L-
NAME
did not significantly alter the immediate hypotensive response to captopril but disclosed a later hypertensive reaction. In L-
NAME
+ BKant-treated rats, both the hypotensive response and the late hypertension was abolished. In rats treated with phentolamine + L-
NAME
, the immediate fall in BP was not different from the controls whereas the late hypertension was absent. 5. BKant itself had no effect on basal BP in either WKY or SHR even when a 10 times higher dose was tested in a separate set of experiments. This was true also for conscious, nonnephrectomized SHR rats. 6. It was concluded that endogenous production of bradykinin was demonstrable through kininase II-inhibition in hypertensive but not in normotensive rats. However, this endogenous bradykinin did not play a role in basal BP homeostasis. The captopril-induced hypotension depended on kinin but, under the present conditions, not on NO as a mediator. The fall in BP induced a compensatory adrenergic hypertensive response which was revealed when the continuous NO-synthesis was blocked by L-
NAME
.
...
PMID:The role of endogenous bradykinin in blood pressure homeostasis in spontaneously hypertensive rats. 886 25
We investigated the effects of NG-nitro-L-arginine-methyl ester (L-
NAME
), a nitric oxide synthase (NOS) inhibitor, on bone metastasis of human breast cancer, MDA-231 cells. Tumor cells (2 x 10(5) cells in 0.2 ml of phosphate-buffered saline;
PBS
) were injected through the diaphragm into the left ventricle of the heart of laparotomized nude mice (male 5-week-old ICR-nu/nu). L-
NAME
(2 mg/mouse/injection in 0.1 ml of
PBS
) was given intraperitoneally to mice 6 h and 3 h before and immediately, 3 h, 6 h, 18 h and 21 h after the intracardiac injection of tumor cells. As a control, 0.1 ml of
PBS
was injected instead of L-
NAME
. The effect of NG-nitro-D-arginine-methyl ester (D-
NAME
; 2 mg/mouse/injection), an inactive analogue of L-
NAME
, was also investigated to evaluate the specificity of L-
NAME
action. Radiographical examination 31 days after the tumor-cell injection showed that the incidence and number of osteolytic bone metastases and the number of bones with metastasis in L-
NAME
-treated mice were significantly reduced compared with those in
PBS
-treated mice (P < 0.05). The differences between
PBS
-treated and D-
NAME
-treated mice were not significant. Our findings suggest that specific and appropriate NOS inhibitors may represent a new pharmacological approach to therapy for cancer patients at risk of developing osteolytic bone metastases.
...
PMID:NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model. 936 34
We tested the hypothesis that NO synthase inhibition alters proinflammatory cytokine expression during acute lung injury in mice. Five-week-old CD-1 mice were pretreated with l-
NAME
or d-
NAME
and then received an intratracheal injection of endotoxin (or
PBS
). TNF-alpha and IL-6 ELISAs and RT-PCR were performed on lung homogenates sampled 6 h later. l-
NAME
increased TNF-alpha and IL-6 protein and mRNA expression in lungs. Immunostaining demonstrated that TNF-alpha was expressed predominantly by macrophages in the lung. l-
NAME
did not alter pulmonary macrophage concentration. To better understand the effect of NO synthase inhibition, elicited murine peritoneal macrophages were stimulated in vitro with LPS after addition of l-
NAME
, d-
NAME
, nitroprusside, or control. Nuclear proteins were extracted 3 h later and electrophoretic mobility shift and supershift assays were performed using radiolabeled NF-kappaB consensus sequence oligonucleotides. Endotoxin increased NF-kappaB p50/p65 heterodimer binding. Binding was further increased by l-
NAME
and decreased by nitroprusside. The effect of nitroprusside was not blocked by guanylate cyclase inhibition. We conclude that, in endotoxin-induced acute lung injury, NO synthase inhibition increases proinflammatory cytokine protein and mRNA expression in part because NO decreases the amount of NF-kappaB available for binding to the regulatory region of proinflammatory cytokine genes.
...
PMID:Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. 1043 Jul 48
Relaxin promotes growth and softening of the cervix during pregnancy in the rat. This study examined the hypothesis that nitric oxide (NO) mediates the effects of relaxin on the rat cervix. To test that hypothesis, N omega-nitro-L-arginine methyl ester (L-
NAME
) was used to inhibit NO synthase, the enzyme that converts arginine to NO and L-citrulline. Nonpregnant rats were ovariectomized when they were 78 days old (day 1 of treatment). At ovariectomy each animal was fitted with silicon tubing implants containing progesterone (P) and estrogen (E) in doses that provide blood levels similar to those during late pregnancy. Rats were assigned to three treatment groups. The control group OPE (n = 6 rats) received 0.5 ml L-
NAME
vehicle (
PBS
) sc at 6-h intervals from 0600 h on day 7 through 1200 h on day 8 and 0.5 ml relaxin vehicle (
PBS
) sc at 0600 and 1200 h on day 8. Group OPER (n = 6 rats) was treated in the same way as group OPE, except that 20 microg porcine relaxin were administered. Group OPERI (n = 7 rats) was treated in the same way as group OPER, except that L-
NAME
was administered at a dose of 100 mg/kg x 6 h. Between 1400-1500 h on day 8, the cervices were removed and weighed. Cervical wet weight and extensibility were markedly greater (P < 0.01) in relaxin-treated group OPER rats than in group OPE controls. Treatment with L-
NAME
diminished relaxin's effects on cervical wet weight, but not cervical extensibility. In conclusion, this study provides evidence that NO contributes to the acute effects of relaxin on the growth, but not the softening, of the rat cervix.
...
PMID:Inhibition of nitric oxide synthase activity diminishes the acute effects of relaxin on growth, but not softening, of the cervix in the rat. 1087 46
Experiments were performed in male Sprague-Dawley rats (150-200 g). A silver clip (0.2 mm internal diameter) was placed on the left renal artery of rats. After operation the rats were divided into 4 groups sham group, 2K1C (two-kidney one clip) group, 2K1C+Arg (2K1C and L-Arg 150 mg/kg x d(-1) by drinking) group, and 2K1C+NAME (2K1C and L-
NAME
10 mg/kg x d(-1) i.p.) group. The animals were studied at two time points (4 and 7 weeks after operation) corresponding to phases I and II of Goldblatt hypertension. The animals were deeply anesthetized with pentobarbital and perfused by the cardiac route with saline (100 ml) and freshly prepared 4% paraformaldehyde in phosphate buffer (300 ml). The caudal medulla was removed, then placed in 25% sucrose in PB for 12 h in a 4 degrees C fridge. The 40 microm coronal slices of brainstems were cut with cryostat, collected in
PBS
for nNOS study by immunohistochemistry. The results showed that (1) only a few neuronal nitric oxide synthase (nNOS) positive neurones were found in caudal medulla, including the depressor area of the ventral surface of medulla oblongata (VSMd) and the caudal pressor area (CPA) of the sham operated animals. The number of nNOS positive neurons in caudal medulla was significantly increased in 2K1C Goldblatt hypertension rats at 4 and 7 weeks. (2) The number of nNOS positive neurons in VSMd and CPA were 2K1C+Arg > 2K1C >2K1C +NAME > sham. (3) L-Arg enhanced the expression of nNOS whereas L-
NAME
inhibited the expression of nNOS in caudal medulla. (4) The character of nNOS expression was similar in Goldblatt hypertension rats at 4 weeks with that of the rats at 7 weeks.
...
PMID:[The expression of neuronal nitric oxide synthase in caudal medulla of two-kidney one clip Goldblatt hypertension rat]. 1197 1
NADPH-diaphorase activity has been considered as a nitric oxide synthase (NOS) marker. Therefore, the presence of NADPH-d activity in Entamoeba histolytica suggests that they have NOS activity. The aim of this work was to provide support for this contention. The amebic culture medium or amebic purified proteins induced relaxation of endothelium-denuded rat aortic rings pre-contracted with phenylephrine (10(-6) M), which was inhibited when the amebas were incubated with NG-monomethyl-L-arginine or aminoguanidine (NOS inhibitors), or by pretreatment of the aortic rings with methylene blue. L-Arginine reverted the L-
NAME
inhibitory effect. In addition, trophozoites produce NO in culture and they have proteins which were recognized by antibodies specific to NOS and show activity of NO synthase. In conclusion, our results provide evidence about the production of NO by trophozoites. This molecule may be responsible for the relaxation elicited by the amebic culture medium and may participate in the pathogenesis of the invasive amebiasis. Index Descriptors and Abbreviations: Entamoeba histolytica; NO, nitric oxide; NOS, nitric oxide synthase; iNOS, inducible nitric oxide synthase; ecNOS, endothelial nitric oxide synthase; NADPH-d, NADPH-diaphorase enzyme; beta-NADPH, beta-nicotinamide-adenine dinucleotide; L-
NAME
, N-omega-nitro-L-arginine methyl ester hydrochloride; NBT, nitobluetetrazolium;
PBS
, phosphate-buffered saline; EDTA, ethylenediaminetetraacetic acid; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis
...
PMID:Nitric oxide synthase in Entamoeba histolytica: its effect on rat aortic rings. 1455 55
To investigate the role of nitric oxide in controlling endothelial progenitor (EPC) and hematopoietic stem cell (HSC) mobilization, wild-type mice, L-
NAME
treated WT and eNOS-/- mice received either
PBS
or G-CSF for 5 days. Under unstimulated conditions bone marrow of either L-
NAME
treated WT and eNOS-/- mice, representing acute and chronic NO-deficiency, showed higher CD34(+)Flk-I+ EPC numbers compared to their WT littermates. Furthermore, CD34(+)Flk-I+ progenitors under NO-deficient conditions showed a higher cell turn over since the proliferation and apoptosis activity under in vivo as well as in vitro conditions were enhanced. In line with this finding bone marrow derived EPC differentiation towards endothelial cells was modulated in an NO-dependent manner. Administration of G-CSF resulted in an increase of EPC within the bone marrow of WT animals with a consecutive release of these cells into the peripheral circulation. Under NO-deficient conditions G-CSF failed to increase EPC numbers. In contrast, the HSC population c-kit(+)Lin- was not influenced by nitric oxide. Thus, NO differentially supports the mobilization of the endothelial committed progenitor subpopulation in bone marrow but does not have an effect on HSC in vivo.
...
PMID:Nitric oxide differentially regulates proliferation and mobilization of endothelial progenitor cells but not of hematopoietic stem cells. 1627 Jun 28
Erythropoietin (EPO), a pleiotropic cytokine involved in erythropoiesis, is tissue-protective in ischemic, traumatic, toxic and inflammatory injuries. In this study, we investigated the effect of EPO in experimental intracerebral hemorrhage (ICH). Two hours after inducing ICH via the stereotaxic infusion of collagenase, recombinant human EPO (500 or 5000 IU/kg, ICH + EPO group) or
PBS
(ICH + vehicle group) was administered intraperitoneally, then once daily afterwards for 1 or 3 days. ICH + EPO showed the better functional recovery in both rotarod and modified limb placing tests. The brain water content was decreased in ICH + EPO dose-dependently, as compared with ICH + vehicle. The effect of EPO on the brain water content was inhibited by N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-
NAME
, 10 mg/kg). Mean hemorrhage volume was also decreased in ICH + EPO. EPO reduced the numbers of TUNEL +, myeloperoxidase + or OX-42 + cells in the perihematomal area. In addition, EPO reduced the mRNA level of TNF-alpha, Fas and Fas-L, as well as the activities of caspase-8, 9 and 3. EPO treatment showed up-regulations of endothelial nitric oxide synthase (eNOS) and p-eNOS, pAkt, pSTAT3 and pERK levels. These data suggests that EPO treatment in ICH induces better functional recovery with reducing perihematomal inflammation and apoptosis, coupled with activations of eNOS, STAT3 and ERK.
...
PMID:Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage. 1653 88
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
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