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)

In a search for airway epithelial mechanisms that may affect the subepithelial microcirculation, we examined plasma exudation responses to NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. L-NAME was applied topically on the tracheal mucosa of guinea pigs that had previously received 125I-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was determined by the levels of 125I-albumin in tracheal lavage fluid. Topical L-NAME (2.2, 9, and 22 mumol), but not intravenous L-NAME (375 mumol/kg), produced plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The L-NAME enantiomer NG-nitro-D-arginine-methyl ester (D-NAME, 9 mumol) produced no exudative response. Coadministration of L-arginine (27 mumol) abolished the L-NAME-induced exudation. The extravasated plasma was distributed in the lamina propria and between epithelial cells (colloidal gold). The epithelial surface structure (scanning electron microscopy) appeared intact. Staining with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase suggested that epithelial basal may contain nitric oxide synthases. We suggest that endogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the subepithelial microcirculation.
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PMID:Mucosal nitric oxide may tonically suppress airways plasma exudation. 802 53

The role of nitric oxide (NO) in the gastric mucosal blood flow response and the healing of HCl-induced gastric lesions was investigated in rats. After 18 h fasting rats were given 0.6 N HCl p.o. for the induction of gastric lesions, and 1 h later they were fed normally. After induction of gastric lesions, they were repeatedly administered the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 5-20 mg/kg p.o. twice daily) or aminoguanidine (20 mg/kg s.c. once daily) for 7 days. Gastric lesions caused by HCl healed almost completely within 5 days with granulation and to an extent with re-epithelialization. Repeated administration of L-NAME but not aminoguanidine significantly delayed the healing of gastric lesions in a dose-dependent manner. The damaged mucosa secreted less acid, but showed a marked rise in H+ permeability, resulting in luminal acid loss accompanied by an increase of mucosal blood flow. Aminoguanidine did not significantly affect any of these functional changes observed in the stomach after damage by HCl, whereas L-NAME treatment slightly reversed the decreased acid response, increased the luminal H+ loss, and totally inhibited the mucosal hyperemic response associated with luminal acid loss in the damaged mucosa. In addition, the deleterious influences of L-NAME on the mucosal blood flow response and the healing of gastric lesions were significantly antagonized by co-administration of L-arginine but not of D-arginine (500 mg/kg x 2, i.p.). Luminal output of NO2-/NO3- was significantly increased in pylorus-ligated stomachs in control rats on days 3 and 5 after damage, and such increases in gastric NO output were completely attenuated by L-NAME treatment. These results suggest that endogenous NO may contribute to the healing of acute gastric injury by mediating the mucosal hyperemic responses associated with acid back-diffusion and by facilitating acid disposal in the damaged mucosa. NO mediating such responses and participating in the healing aspect of gastric lesions may be produced by the constitutive type of NO synthase.
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PMID:Role of nitric oxide in mucosal blood flow response and the healing of HCl-induced lesions in the rat stomach. 901 6

The effects of pharmacological modulation of the nitric oxide (NO) pathway on intestinal fluid transport were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Close intraarterial infusion of 5-hydroxytryptamine (5-HT) (0.16 microg/min) induced net fluid secretion. Intravenous infusion of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (0.55 mg/kg per min) reversed net fluid absorption in controls to net secretion and significantly enhanced 5-HT-induced fluid secretion. 5-HT-induced net fluid secretion was inhibited by intravenous infusion of L-arginine (8.88 mg/kg per min), sodium nitroprusside (22.2 microg/kg per min), or 3-morpholino sydnonimine (SIN-1) (22.2 microg/kg per min). Intraluminal instillation of cholera toxin (0.5 microg/ml) induced net secretion, which was significantly enhanced by L-NAME and reduced by L-arginine. Another series of experiments was performed using a model of luminally perfused jejunal loops. Cholera toxin (10 microg/ml) induced profuse net fluid secretion also in this model. L-Arginine and sodium nitroprusside significantly enhanced net fluid absorption compared to controls and abolished the secretory effect of cholera toxin. Luminal perfusion with oral rehydration solution enhanced net absorption of fluid in controls and reversed cholera toxin-induced secretion to absorption. Intravenous infusion, but not intraluminal administration, of L-arginine significantly enhanced the antisecretory effect of oral rehydration solution. These results give further support to the existence of an intestinal NO-mediated proabsorptive tone, which also downregulates fluid secretion elicited by different enterotoxins or mediators of secretion. Intravenous administration of exogenous sources of NO counteracts intestinal fluid accumulation and augments the antisecretory effect of oral rehydration solution, findings which may lead to therapeutic consequences.
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PMID:Nitric oxide counteracts 5-hydroxytryptamine- and cholera toxin-induced fluid secretion and enhances the effect of oral rehydration solution. 919 75

The aim of the study was to determine if and by what mechanism(s) nitric oxide inhibition modulates the susceptibility of the duodenum to hydrochloric acid-induced disturbances of mucosal integrity. A second aim was to investigate whether basal permeability is a determinant of epithelial acid barrier function. Using an in situ duodenal perfusion model, mucosal permeability, alkaline secretion and morphology were investigated in anaesthetized rats. Luminal perfusion with 50 mM hydrochloric acid increased duodenal mucosal permeability in the control animals. In animals receiving the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME 3 mg kg(-1) and 1 mg kg(-1) h(-1)) and in those receiving vasopressin (1 IU kg(-1) h(-1)), however, the mean increase in permeability in response to acid was markedly higher. In rats treated with either hexamethonium (20 mg kg(-1)) or atropine (0.5 mg kg(-1)) L-NAME failed to augment the acid-induced increase in permeability. Perfusion with hypotonic saline (25 mM) increased basal permeability but did not influence the response to acid. Exposure of the duodenum to hydrochloric acid caused very subtle changes of duodenal morphology. It is concluded that both inhibition of endogenous nitric oxide synthesis and vasopressin treatment augment the acid-induced increase in mucosal permeability. The mechanisms involved may be related to changes of Starling forces in the microcirculatory bed. Endogenous nitric oxide may protect the duodenal mucosa by regulating vascular permeability and interstitial fluid pressure.
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PMID:Acid-induced increase in duodenal mucosal permeability is augmented by nitric oxide inhibition and vasopressin. 933 17

Gender differences in the incidence of stroke and migraine appear to be related to circulating levels of estrogen; however, the underlying mechanisms are not yet understood. Using resistance-sized arteries pressurized in vitro, we have found that myogenic tone of rat cerebral arteries differs between males and females. This difference appears to result from estrogen enhancement of endothelial nitric oxide (NO) production. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (Ovx), or ovariectomized with estrogen replacement (Ovx + Est). The maximal passive diameters (0 Ca2+ + 1 mM EDTA) of arteries from all four groups were identical. In response to a series of 10-mmHg step increases in transmural pressure (20-80 mmHg), myogenic tone was greater and vascular distensibility less in arteries from males and Ovx females compared with arteries from either untreated or Ovx + Est females. In the presence of NG-nitro-L-arginine methyl ester (L-NAME; 1 microM), an NO synthase inhibitor, myogenic tone was increased in all arteries, but the differences among arteries from the various groups were abolished. Addition of L-arginine (1 mM) in the presence of L-NAME restored the differences in myogenic tone, suggesting that estrogen works through an NO-dependent mechanism in cerebral arteries. To determine the target of NO-dependent modulation of myogenic tone, we used tetraethylammonium (TEA; 1 mM) to inhibit large-conductance, calcium-activated K+ (BKCa) channels. In the presence of TEA, the myogenic tone of arteries from all groups increased significantly; however, myogenic tone in arteries from males and Ovx females remained significantly greater than in arteries from either untreated or Ovx + Est females. This suggests that activity of BKCa channels influences myogenic tone but does not directly mediate the effects of estrogen. Estrogen appears to alter myogenic tone by increasing cerebrovascular NO production and/or action.
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PMID:Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries. 968 26

Nitric oxide has been shown to be an inhibitory neurotransmitter in the mammalian colon, although its role in colonic transit remains unclear. We investigated the effect of the nitric oxide biosynthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on colonic transit in conscious rats. Colonic transit was determined by calculating the geometric center of the distribution of radiochromium instilled into the proximal colon. We also studied the effect of L-NAME on colonic motility in vivo and on descending relaxation in vitro. L-NAME (10 mg/kg) significantly delayed colonic transit compared with saline. The inhibitory effect of L-NAME was prevented by L-arginine (100 mg/kg) but not by D-arginine (100 mg/kg). L-NAME (10 mg/kg) induced random and uncoordinated phasic contractions throughout the rat colon in vivo. Luminal distension evoked descending relaxation in the proximal and distal rat colon in vitro. L-NAME (10(-4) M) significantly inhibited this relaxation. It is suggested, therefore, that nitric oxide enhances transit in the rat colon by mediating descending relaxation, which, in turn, facilitates propulsion of the colonic contents.
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PMID:Nitrergic regulation of colonic transit in rats. 1044 40

In gastric mucosal injury, nitric oxide (NO) plays both cytoprotective and cytotoxic roles, and the NO level is one determinant of these dual roles. We employed electron paramagnetic resonance (EPR)-spectrometry combined with an NO-trapping technique to directly evaluate NO production in ethanol-induced gastric injury in rats. The rat stomach, mounted on an ex vivo chamber, was perfused with ethanol (12.5 and 43%), and NO levels in mucosal tissues were measured during perfusion. Luminal nitrite/nitrate (NOx) content, mucosal blood flow, area of mucosal injury, transmucosal potential difference (PD), and luminal pH were simultaneously monitored with/without preadministration of the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). NO levels in the gastric tissue increased during ethanol perfusion, and luminal NOx levels increased after the perfusion, accompanying an increase in the area of mucosal injury and changes in physiological parameters. Preadministration of L-NAME aggravated the gastric mucosal damage and suppressed increases in mucosal blood flow in a dose-dependent manner. These results demonstrate that endogenous NO produced in ethanol-induced gastric injury contributes to maintenance of mucosal integrity via regulation of mucosal blood flow.
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PMID:Direct detection of nitric oxide and its roles in maintaining gastric mucosal integrity following ethanol-induced injury in rats. 1265 4

We compared the HCO3(-) secretory response to capsaicin and mucosal acidification in rat duodenums, especially the relation to vanilloid receptor type 1 (VR1). A proximal duodenal loop was perfused with saline, and the HCO3(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. The secretion was stimulated by exposing the loop to capsaicin (0.03-0.3 mg/ml) or 10 mM HCl for 10 min. Indomethacin subcutaneously or ruthenium red intravenously, a nonspecific VR1 antagonist, was given 60 or 10 min, respectively, before exposure to capsaicin or acid, while L-NAME was given intravenously 3 hr before these treatments. Capsazepine, another VR1 antagonist, was coapplied to the loop for 10 min with capsaicin or acid. Luminal application of capsaicin increased the secretion of HCO3(-) in a dose-dependent manner; this effect was markedly attenuated by chemical ablation of capsaicin-sensitive afferent neurons (CSN) as well as pretreatment with ruthenium red or capsazepine, and significantly mitigated by indomethacin or L-NAME (in an L-arginine-sensitive manner). The HCO3(-) secretion was also stimulated by mucosal acidification, and this response was attenuated by both capsaicin pretreatment, indomethacin and L-NAME, but not ruthenium red or capsazepine. Mucosal application of capsaicin as well as acid increased the mucosal PGE2 content, and these effects were both significantly attenuated by indomethacin and L-NAME. These results suggest that both capsaicin and acid cause the CSN-dependent increase in duodenal HCO3(-) secretion mediated by NO and PG, yet the mode of their action differs in terms of the ruthenium red or capsazepine sensitivity. Although luminal H+ plays a modulatory role in duodenal HCO3(-) secretion, it is unlikely that the action results from the interaction of H+ with the ruthenium red- or capsazepine-sensitive site of VR1.
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PMID:Stimulation by capsaicin of duodenal HCO3(-) secretion via afferent neurons and vanilloid receptors in rats: comparison with acid-induced HCO3(-) response. 1456 Oct 13

The present experiments in mice were performed to determine the steady-state effects of exogenous adenosine on the vascular resistance of the whole kidney, of superficial blood vessels, and of afferent arterioles. The steady-state effect of an intravenous infusion of adenosine (5, 10, and 20 microg/min) in wild-type mice was vasodilatation as evidenced by significant reductions of renal and superficial vascular resistance. Resistance decreases were augmented in adenosine 1 receptor (A1AR) -/- mice. Renal vasodilatation by the A2aAR agonist CGS 21680A [2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamido-adenosine hydrochloride] (0.25, 0.5, and 1 microg/kg/min) and inhibition of adenosine-induced relaxation by the A2aAR antagonist ZM-241385 [4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol] (20 mg/kg) suggests that the reduction of renovascular resistance was largely mediated by A2aAR. After treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) adenosine was unable to alter superficial blood flow and resistance significantly indicating that adenosine-induced dilatation is NO-dependent. Absence of a dilatory effect in endothelial nitric-oxide synthase (NOS) -/- mice suggests endothelial NOS as the source of NO. When infused into the subcapsular interstitium, adenosine reduced superficial blood flow through A1AR activation. Adenosine (10(-7) M) constricted isolated perfused afferent arterioles when added to the bath but not when added to the luminal perfusate. Luminal adenosine caused vasoconstriction in the presence of L-NAME or the A2AR antagonist 3,7-dimethyl-1-(2-propynyl)xanthine. Our data show that global elevation of renal adenosine causes steady-state vasorelaxation resulting from adenosine 2 receptor (A2AR)-mediated generation of NO. In contrast, selective augmentation of adenosine around afferent arterioles causes persistent vasoconstriction, indicating A1AR dominance. Thus, adenosine is a renal constrictor only when it can interact with afferent arteriolar A1AR without affecting the bulk of renal A2AR at the same time.
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PMID:Vasoconstrictor and vasodilator effects of adenosine in the mouse kidney due to preferential activation of A1 or A2 adenosine receptors. 1612 Aug 12

Endothelin (ET) and nitric oxide (NO) modulate ion transport in the kidney. In this study, we defined the function of ET receptor subtypes and the NO guanylate cyclase signaling pathway in mediating the adaptation of the rabbit cortical collecting duct (CCD) to metabolic acidosis. CCDs were perfused in vitro and incubated for 3 h at pH 6.8, and bicarbonate transport or cell pH was measured before and after acid incubation. Luminal chloride was reversibly removed to isolate H(+) and HCO(3)(-) secretory fluxes and to raise the pH of beta-intercalated cells. Acid incubation caused reversal of polarity of net HCO(3)(-) transport from secretion to absorption, comprised of a 40% increase in H(+) secretion and a 75% decrease in HCO(3)(-) secretion. The ET(B) receptor antagonist BQ-788, as well as the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME), attenuated the adaptive decrease in HCO(3)(-) secretion by 40%, but only BQ-788 inhibited the adaptive increase in H(+) secretion. There was no effect of inactive d-NAME or the ET(A) receptor antagonist BQ-123. Both BQ-788 and l-NAME inhibited the acid-induced inactivation (endocytosis) of the apical Cl(-)/HCO(3)(-) exchanger. The guanylate cyclase inhibitor LY-83583 and cGMP-dependent protein kinase inhibitor KT-5823 affected HCO(3)(-) transport similarly to l-NAME. These data indicate that signaling via the ET(B) receptor regulates the adaptation of the CCD to metabolic acidosis and that the NO guanylate cyclase component of ET(B) receptor signaling mediates downregulation of Cl(-)/HCO(3)(-) exchange and HCO(3)(-) secretion.
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PMID:Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis. 1670 53


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