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

Studies were carried out to examine the anti-oxidative activity of nitric oxide synthase (NOS) inhibitors including L-N omega-nitro-L-arginine methyl ester (L-NAME) and spermidine in rats pretreated per os with N-nitrosodiethylamine (NDEA) (0.1 mg/kg b.w.) daily for 30 days. Both L-NAME and/or sapermidine were gavaged to animals in a daily dosage of 10 mg/kg body weight, however, the polyamine was applied for the first 21 days only, and further L-NAME was employed for 3 days (day 22, 23 and 24). Saline treated rats were served as control. The results of this experiment showed that NDEA increased TBARS in the liver and small intestine of rats, and the agent did not have any effect(s) in spleen and kidney, respectively. Pretreatment of animals with spermidine and/or L-NAME significantly (p < 0.05) lowered lipid peroxidation in NDEA-treated rats. The finding described here elucidate that both L-NAME and spermidine play an important anti-oxidative role in NDEA-mediated lipid peroxidation and/or pro-oxidant shift(s) in rats.
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PMID:Nitric oxide synthase inhibitors reduced lipid peroxidation in N-nitrosodiethylamine-treated rats. 1155 2

The present study was undertaken to investigate the effect of vitamin C treatment on blood pressure and vascular reactivity in salt-induced hypertension. Male Sprague-Dawley rats were fed a normal rat diet, a high-sodium (8% NaCl) diet, a normal rat diet plus vitamin C treament (100 mg x kg(-1) x day(-1)), or a high-sodium diet plus vitamin C treatment for 6 weeks. Salt loading significantly increased blood pressure, which was attenuated by vitamin C treatment. Aortic rings from the different groups were suspended for isometric-tension recording. The contractile response to noradrenaline was significantly increased in the salt-loaded rats. Vitamin C reduced the sensitivity of aortic rings to noradrenaline in rats on normal and high-sodium diets. In noradrenaline-precontracted rings, the relaxation response to acetylcholine, which was attenuated in the salt-loaded rats, was restored by vitamin C treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) abolished the enhanced response to acetylcholine caused by vitamin C. The results suggest that the antihypertensive effect of vitamin C is associated with a reduction in vascular sensitivity to noradrenaline and enhancement of endothelium-dependent relaxation due to increased nitric oxide bioavailability.
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PMID:Vitamin C lowers blood pressure and alters vascular responsiveness in salt-induced hypertension. 1256 47

We examined the effects of inhibiting nitric oxide synthase with Nomega-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU.min-1.kg-1) significantly increased hindlimb total blood flow (0.69 +/- 0.02 to 1.22 +/- 0.11 ml/min, P < 0.05), glucose uptake (0.27 +/- 0.05 to 0.95 +/- 0.08 micromol/min, P < 0.05), 1-MX uptake (5.0 +/- 0.5 to 8.5 +/- 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 +/- 1.6 to 15.0 +/- 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% (P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.
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PMID:Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin. 1279 3

We tested the hypothesis that inhibition of synthesis of either nitric oxide (NO) or vasodilating prostaglandins (PGs) would not alter exercise hyperaemia significantly, but combined inhibition would synergistically reduce the hyperaemia. Fourteen subjects performed 20 min of moderate rhythmic forearm exercise (10% maximal voluntary contraction). Forearm blood flow (FBF) was measured by Doppler ultrasound. Saline or study drugs were infused (2 ml x min(-1)) into the forearm via a brachial artery catheter to locally inhibit synthesis of NO and PGs during steady state exercise (N(G)-nitro-L-arginine methyl ester (L-NAME), 25 mg over 5 min to inhibit NO synthase (NOS); and ketorolac, 3 mg over 5 min to inhibit cyclooxygenase (COX)). After achieving steady state exercise over 5 min (control), L-NAME was infused for 5 min, followed by 2 min saline, then by a 5 min infusion of ketorolac, and finally by 3 min of saline (n= 7). Drug order was reversed in seven additional subjects, such that single inhibition of NOS or COX was followed by combined inhibition. FBF during exercise decreased to 83 +/- 2% of control exercise (100%) with NOS inhibition, followed by a transient decrease to 68 +/- 2% of control during COX inhibition. However, FBF returned to levels similar to those achieved during NOS inhibition within 2 min (80 +/- 3% of control) and remained stable through the final 3 min of exercise. When COX inhibition was performed first, FBF decreased transiently to 88 +/- 4% of control (P < 0.01), and returned to control saline levels by the end of ketorolac infusion. Addition of L-NAME reduced FBF to 83 +/- 3% of control, and it remained stable through to the end of exercise. Regardless of drug order, FBF was approximately 80% of steady state control exercise (P < 0.01) during the last 30 s of exercise. We conclude that (1). NO provides a significant, consistent contribution to hyperaemia, (2). PGs contribute modestly and transiently, suggesting a redundant signal compensates for the loss of vasodilating PGs, and (3). NO and PG signals appear to contribute independently to forearm exercise hyperaemia.
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PMID:Local inhibition of nitric oxide and prostaglandins independently reduces forearm exercise hyperaemia in humans. 1510 76

The present study evaluated the role of nitric oxide (NO) in the transfer latency (TL) paradigm in the elevated plus-maze. Male Wistar rats received i.p. injections of either 0.9% Saline, N(omega) Nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of NO synthesis), d-NAME (inert isomer), scopolamine (SCO, antagonist of muscarinic receptors), or MK-801 (antagonist of NMDA receptors) and, after 30 min, were submitted to TL procedure. In an independent experiment, the ability of the same L-NAME treatments in changing the arterial pressure and blood glucose level (BGL) was evaluated in conscious rats. The treatment with SCO (1 mg kg(-1)), MK-801 (0.15 mg kg(-1)) and L-NAME (10 and 50 mg kg(-1)), but not with D-NAME, impaired the TL learning. The L-NAME-induced TL deficit was counteracted by L-ARG (100 and 200 mg kg(-1)), while the co-administration of sub-effective doses of L-NAME and MK-801 failed to impair the TL learning. The L-NAME (50 mg kg(-1)) treatment failed to alter the BGL. All treatments with L-NAME induced hypertension, but the rats treated with L-NAME (5 mg kg(-1)) were still able to learn the TL task. The data indicate that the TL deficit induced by L-NAME (10 and 50 mg kg(-1)) is not due to either hypertension or changes in the BGL. It is also possible to establish that NO production is important for emotional learning underlying the TL procedure in rats.
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PMID:The role of nitric oxide in the emotional learning of rats in the plus-maze. 1576 71

High salt intake is involved in the genesis of hypertension and vascular changes in salt-sensitive patients. Although many mechanisms have been proposed, the underlying mechanisms of these alterations in healthy rats are not completely elucidated. The aim of this study was to investigate if male Wistar rats fed a high salt diet, NaCl 1.8% in drinking water for 4 weeks, develop changes in the pressor reactivity of isolated tail and renal vascular beds. Salt treatment increased mean arterial pressure (SALT = 124 +/- 2.2 vs. CT = 111 +/- 3.9 mmHg; p < 0.01) and urinary sodium excretion in the absence of changes in sodium plasma levels. Pressor reactivity was generated in isolated tail and kidney vascular beds as dose-response curves to phenylephrine (PHE = 0.01 to 300 microg). SALT increased the reactivity (E(max): SALT = 378 +/- 15.8 vs. CT = 282 +/- 10 mmHg; p < 0.01) without changing the sensitivity (pD(2)) to PHE in the tail vascular bed. However, these parameters did not change in the renal bed. In subsequent studies on the isolated caudal vascular bed, we found that endothelial damage, but not L-NAME (100 microM) or indomethacin (10 microM), abolished the increment in E(max) to PHE induced by SALT. On the other hand, losartan (100 microM) reduced E(max) in SALT to CT values. Additionally, local angiotensin-converting enzyme activity in segments from tail artery increased by 95%. In conclusion, 4 weeks of high salt diet increases blood pressure and induces specific territorial vascular changes in response to PHE. Results also suggest that the increment in E(max) in the tail vascular bed from SALT rats was endothelium-dependent and was mediated by the activation of the local renin-angiotensin system.
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PMID:Effects of high sodium intake diet on the vascular reactivity to phenylephrine on rat isolated caudal and renal vascular beds: Endothelial modulation. 1628 40

Nitric oxide (NO) involvement in intestinal ischemia-reperfusion (I/R) injury has been widely suggested but its protective or detrimental role remains still question of debate. Here, we examine the impact of supplementation or inhibition of NO availability on intestinal dysmotility and inflammation caused by mesenteric I/R in mice. Ischemia 45min and reperfusion 24h were performed by superior mesenteric artery occlusion in female Swiss mice. Saline-treated sham-operated (S) or normal mice without surgery (N) served as controls. Drugs were subcutaneously injected 0, 4, 8, and 18 h after ischemia. Upper gastrointestinal transit (GIT, estimated through black marker gavage), intestinal myeloperoxidase activity (MPO), intestinal malondialdehyde levels (MDA), Evans blue extravasation (EB), intestinal histological damage, and mean arterial pressure (MAP) were considered. In I/R mice, GIT was significantly delayed compared to S and N groups; MPO activity and EB extravasation enhanced, whereas MDA levels did not change. Compared to N and S groups, in I/R mice selective iNOS inhibitor P-BIT significantly prevented motor, MPO and EB changes; putative iNOS inhibitor aminoguanidine significantly counteracted GIT delay but not neutrophil recruitment and the increase in vascular permeability; NOS inhibitor l-NAME and NO precursor l-arginine were scarcely or no effective. Furthermore, in S mice aminoguanidine caused a significant increase of MPO activity reverted by H(1) histamine receptor antagonist pre-treatment. Unlike P-BIT, aminoguanidine and l-NAME injection increased MAP. These findings confirm a detrimental role for iNOS-derived NO overproduction during reperfusion. Aminoguanidine-associated neutrophil recruitment suggests that this drug could act through mechanisms additional to iNOS inhibition involving both eNOS blockade, as indicated by its hemodynamic effects, and indirect activation of H(1) histamine receptors.
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PMID:The selective inhibition of inducible nitric oxide synthase prevents intestinal ischemia-reperfusion injury in mice. 1650 57

Glutamate N-methyl-d-aspartate (NMDA) receptors and the enzyme neuronal nitric oxide synthase (nNOS) are significantly expressed in the midbrain dorsolateral periaqueductal gray (dlPAG). Local injections of either NMDA-receptor agonists or nitric oxide (NO) donors induce flight reactions in rats. Since the activation of NMDA receptors in the brain increases the synthesis of NO, the present work was conducted to test the hypothesis that the flight reaction induced by intra-dlPAG administration of NMDA would be mediated by endogenous NO. Male Wistar rats with cannulas aimed at the dlPAG received intracerebral injections of l-NAME (NOS inhibitor, 100-200 nmol), carboxy-PTIO (NO scavenger, 1-3 nmol) or ODQ (guanylate cyclase inhibitor, 1-3 nmol). Saline or NMDA (0.1 nmol) was injected 10 min later and the behavioral changes were recorded for 2 min in the injection box. Intra-dlPAG injection of NMDA produced flight reactions characterized by crossings and jumps. Contrary to the initial hypothesis, these effects were not prevented by pretreatment with l-NAME, carboxy-PTIO or ODQ. Although the NO pathway may mediate some effects induced by NMDA receptor activation in the brain, the present results suggest that the administration of NMDA into the dlPAG induces flight reactions by mechanisms that are independent of endogenous NO.
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PMID:Flight reactions induced by injection of glutamate N-methyl-d-aspartate receptor agonist into the rat dorsolateral periaqueductal gray are not dependent on endogenous nitric oxide. 1654 44

Cutaneous vascular conductance (CVC) declines in response to local cooling (LC). Previous work indicates that at least part of the vasoconstrictor response to LC may be through an inhibitory effect on nitric oxide synthase (NOS) activity. In this study we further tested that notion. A total of eight (6 male, 2 female) subjects participated (Part 1 n = 7; Part 2 n = 5, 4 of whom participated in Part 1). Skin blood flow was monitored by laser-Doppler flowmetry. Control of local skin and body temperatures was achieved with Peltier cooler/heater probe holders and water perfused suits, respectively. Microdialysis fibres were inserted aseptically. Saline, L-NAME (20 mM; to inhibit NOS activity) and sodium nitroprusside (SNP 10 microM) were infused by microdialysis. Bretylium tosylate (BT), to block adrenergic function, was administered by iontophoresis. CVC was calculated from blood flow and blood pressure. Part 1 was designed to determine the relative roles of the NO and the adrenergic systems. The infusion of L-NAME elicited a 35 +/- 4% decrease in CVC at the L-NAME and BT + L-NAME sites (P < 0.05); subsequent slow LC (34-24 degrees C) for 35 min caused a significant (P < 0.05) decrease in CVC at control sites (68 +/- 4%) and at the BT treated sites (39 +/- 5%). LC caused a further 23 +/- 5% of initial baseline decrease in CVC at the L-NAME treated sites (P < 0.05). Importantly, CVC at the BT + L-NAME sites was unaffected by LC (P > 0.05). Part 2 was designed to test whether LC influences were specific to the NOS enzymes. Two sites were pretreated with both BT and L-NAME. After 50 min, SNP was added as an NO donor to restore baseline CVC at one site. The same LC process as in Part 1 was applied. There was a 24 +/- 10% decrease (P < 0.05) in CVC at sites with baseline CVC restored, while, as in Part 1, there was no change (P > 0.05) at sites treated with BT + L-NAME only. These data suggest that the vasoconstriction with slow LC is due to a combination of increased noradrenaline release and decreased activity of both NOS per se and of process(es) downstream of NOS.
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PMID:The involvement of nitric oxide in the cutaneous vasoconstrictor response to local cooling in humans. 1672 51

Estrogen stimulates endothelial nitric oxide (NO) production and attenuates endothelial dysfunction in ischemia/repurfusion and menopause. Recent studies have shown that phytoestrogens from dietary sources improve endothelial function and reduce cardiovascular risks. The Thai medicinal plant Pueraria mirifica (PM) contains many potent phytoestrogens including miroestrol and deoxymiroestrol but no study on vascular function has been established. Ground powder of PM was orally given to ovariectomized White New Zealand rabbits (OVX + PM group) (n = 4) weighing 3.2-4.0 kg at the dose of 100 mg/kg for 90 days. Saline-treated ovariectomized rabbits were assigned as a control group (OVX group) (n = 5). At the end of treatment thoracic aorta was isolated for functional evaluation. Maximal relaxant response to acetylcholine (ACh) was significantly increased (24%) with 3.5-fold decrease in EC50 while no change in relaxant response to sodium nitroprusside was observed Minimal and maximal responses to 17beta-estradiol (E2) were increased in the OVX + PM group and L-NAME (100 mM) attenuated Emax of E2. PM significantly decreased maximal contractile responses to norepinephrine (NE), but no change in EC50 was observed. In addition to vascular study, the authors found no significant alteration in serum cholesterol, LDL, triglyceride, HDL, ALT AST alkaline phosphatase, and lipid peroxidation in OVX + PM rabbits. These data demonstrate that PM (100 mg/kg/d) improved endothelial function through NO-dependent pathway and increased response to E2 while sensitivity to NE was reduced. In addition, it had no impact on lipid profile, liver enzymes, and ALP activities. PM is a potential source of phytoestrogens for postmenopausal women to improve cardiovascular function or reduce cardiovascular risks.
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PMID:Effects of Pueraria mirifica on vascular function of ovariectomized rabbits. 1686 67


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