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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain. It has been reported that NI plays an important role in integration of CO2 chemoreceptor information and glutamate is probably involved in this function. However, very little is known about the mechanisms involved. Recently, it has been shown that nitric oxide synthase (NOS) is expressed in the brain of the frog. Thus the gas nitric oxide (NO) may be involved in different functions in the brain of amphibians and may act as a neurotransmitter or neuromodulator. We tested the hypothesis that NO plays a role in CO2-drive to breathing, specifically in the NI comparing pulmonary ventilation, breathing frequency and tidal volume, after microinjecting 100 nmol/0.5 microl of L-NAME (a nonselective NO synthase inhibitor) into the NI of toads (Bufo paracnemis) exposed to normocapnia and hypercapnia. Control animals received microinjections of vehicle of the same volume. Under normocapnia no significant changes were observed between control and L-NAME-treated toads. Hypercapnia caused a significant (P<0.01) increase in ventilation only after intracerebral microinjection of L-NAME. Exposure to hypercapnia caused a significant increase in breathing frequency both in control and L-NAME-treated toads (P<0.01 for the control group and P<0.001 for the L-NAME group). The tidal volume of the L-NAME group tended to be higher than in the control group under hypercapnia, but the increase was not statistically significant. The data indicate that NO in the NI has an inhibitory effect only when the respiratory drive is high (hypercapnia), probably acting on tidal volume. The observations reported in the present investigation, together with other studies on the presence of NOS in amphibians, indicate a considerable degree of phylogenetic conservation of the NO pathway amongst vertebrates.
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PMID:Participation of nitric oxide in the nucleus isthmi in CO2-drive to breathing in toads. 1055 41

After abdominal surgery, luminal HCl fails to induce duodenal contractions in anaesthetized rats. Elevated tissue levels of nitric oxide (NO) and prostaglandins possibly contribute to this observation. The aim of this study was to compare the effects of luminal capsaicin (1.2 mg mL-1), ethanol (15%) and high partial pressure of CO2 (>250 mmHg) with those of HCl (10 mM) in anaesthetized rats. Motility (intraluminal pressure), mucosal permeability [blood-to-lumen clearance of 51Cr-EDTA (51Chromium-labelled ethylenediaminetetraacetate)] and duodenal mucosal bicarbonate secretion (DMBS) were recorded. Three groups of animals were studied: (1) controls, (2) pretreatment with the NO synthase inhibitor N-nitro-L-arginine-methyl-ester (L-NAME) and (3) pretreatment with the cyclo-oxygenase inhibitor indomethacin. Neither capsaicin, ethanol, CO2 nor HCl induced duodenal contractions or affected DMBS in control rats. However, L-NAME induced duodenal contractions that were augmented by capsaicin, ethanol and HCl, but not by CO2. Indomethacin also induced contractions that were reversibly diminished by capsaicin and HCl, but not by ethanol or CO2. Significant increases in mucosal permeability occurred during ethanol perfusion in indomethacin- and L-NAME pretreated rats. In conclusion, NO probably plays a key role in preventing duodenal contractions in response to luminally HCl, capsaicin and ethanol. The HCl-induced effect on motility appears to be independent of CO2 and is not caused by alteration in mucosal integrity.
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PMID:Nitric oxide prevents rat duodenal contractions induced by potentially noxious agents. 1088 38

Inhaled carbon dioxide decreases ventilation/perfusion ratio (V'/Q') heterogeneity in dogs. The aim of this study was to test whether inhaled CO2 improves the V'/Q' by inhibition of nitric oxide production and whether inhibition of endogenous NO production in the lung alters gas exchange and V'/Q' matching. Eleven healthy dogs were anaesthetized and mechanically ventilated. The multiple inert gas elimination technique (MIGET) was used to measure V'/Q' heterogeneity and regional pulmonary blood flow heterogeneity was assessed in five dogs using fluorescent microspheres. In a separate set of five dogs, exhaled NO levels were measured via chemiluminescence. All dogs were studied before and after 4.8% inspired CO2, and then given the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg x kg(-1)) via nebulization, after which they were studied again with room air and inhaled CO2. CO2 and L-NAME improved arterial and alveolar oxygen tension, but the improvements with L-NAME did not reach statistical significance. Improved V'/Q' matching, as assessed by the MIGET, occurred under all experimental conditions. Exhaled NO levels were reduced by 40% with CO2 and 70% with L-NAME. The standard deviation of regional pulmonary blood flow assessed via microspheres decreased only with inhaled CO2. Fractal analysis of pulmonary blood flow distributions revealed that regional blood flow was highly correlated with flow to neighbouring pieces of lung in all four conditions with no changes in the fractal dimension. Inspired carbon dioxide improves ventilation perfusion ratio matching and is associated with a more homogeneous distribution of pulmonary blood flow. Although inspired carbon dioxide causes a reduction in exhaled nitric oxide, the differences in pulmonary perfusion distributions found between carbon dioxide and N(omega)-nitro-L-arginine methyl ester suggest that the carbon dioxide effect is not mediated by a reduction in nitric oxide production. The improved ventilation perfusion ratio matching with inhibition of nitric oxide synthase suggests the intriguing possibility requiring further study that endogenous production of nitric oxide in the lung does not subserve ventilation perfusion ratio regulation.
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PMID:Pulmonary NO synthase inhibition and inspired CO2: effects on V'/Q' and pulmonary blood flow distribution. 1096 5

The effect of L-arginine on transepithelial ion transport was examined in cultured M-1 mouse renal cortical collecting duct (CCD) cells using continuous short circuit current (Isc) measurements in HCO3-/CO2 buffered solution. Steady state Isc averaged 73.8 +/- 3.2 microA/cm2 (n = 126) and was reduced by 94 +/- 0.6% (n = 16) by the apical addition of 100 microM amiloride. This confirms that the predominant electrogenic ion transport in M-1 cells is Na+ absorption via the epithelial sodium channel (ENaC). Experiments using the cationic amino acid L-lysine (radiolabeled) as a stable arginine analogue show that the combined activity of an apical system y+ and a basal amino acid transport system y+L are responsible for most cationic amino acid transport across M-1 cells. Together they generate net absorptive cationic amino acid flux. Application of L-arginine (10 mM) either apically or basolaterally induced a transient peak increase in Isc averaging 36.6 +/- 5.4 microA/cm2 (n = 19) and 32.0 +/- 7.2 microA/cm2 (n = 8), respectively. The response was preserved in the absence of bath Cl- (n = 4), but was abolished either in the absence of apical Na+ (n = 4) or by apical addition of 100 microM amiloride (n = 6). L-lysine, which cannot serve as a precursor of NO, caused a response similar to that of L-arginine (n = 4); neither L-NMMA (100 microM; n = 3) nor L-NAME (1 mM; n = 4) (both NO-synthase inhibitors) affected the Isc response to L-arginine. The effects of arginine or lysine were replicated by alkalinization that mimicked the transient alkalinization of the bath solution upon addition of these amino acids. We conclude that in M-1 cells L-arginine stimulates Na+ absorption via a pH-dependent, but NO-independent mechanism. The observed net cationic amino acid absorption will counteract passive cationic amino acid leak into the CCD in the presence of electrogenic Na+ transport, consistent with reports of stimulated expression of Na+ and cationic amino acid transporters by aldosterone.
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PMID:L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium. 1131 95

We examined the effect of NO on acid secretion in vitro using isolated preparations of Bullfrog stomach. The bullfrog fundic mucosa was bathed in unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3- Ringer's solution gassed with 95% O2/5% CO2 on the serosal side, and the acid secretion was measured at pH 5.0 using the pH-stat method and by adding 5 mM NaOH. Serosal addition of a NO donor NOR-3 (10(-5) approximately 10(-3) M: (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine) caused an increase of acid secretion in a dose-dependent manner, the effect lasting about 1 hr and reaching a maximal level of 2-fold the basal values. The acid stimulatory effect of NOR-3 was mimicked by another NO donor SNAP (10(-3) mol/L: S-nitroso-O-N-acetyl-penicillamine) and markedly and markedly inhibited by prior administration of cimetidine (10(-5) mol/L) as well as compound 48/80 (the mast cell degranulator). Likewise, the increased acid response to NOR-3 was significantly mitigatd by pretreatment with carboxy-PTIO (a NO scavenger) or superoxide dismutase (SOD), but not by indomethacin or methylene blue (a guanylyl cyclase inhibitor). Neoither L-NAME, L-arginine nor dibutyryl guanosine-3',5'-cyclic monophosphate (dbcGMP) has any effect on the basal acid secretion. Serosal addition of NOR-3 caused a significant increase in the luminal release of histamine, and this response was inhibited by pretreatment with either compound 48/80, carboxy-PTIO or SOD. These results suggest that the NO donor increases gastric acid secretion in the isolated frog stomach in vitro, and this action is mediated by endogenous histamine released from mast cells, the process being cGMP-independent but requiring the presence of superoxide radicals. In addition, it was speculated that the histamine releasing action of NO may be due to peroxynitrite produced by NO and superoxide radicals.
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PMID:Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro. 1132 16

Endothelial dysfunction associated with both menopause and hypertension could be one of the possible explanations for increased cardiovascular morbidity and mortality in hypertensive postmenopausal women. The aim of the present study was to investigate the long-term effect of menopause (bilateral ovariectomy) on endothelial function in isolated aortic rings of spontaneously hypertensive rats (SHR). Aortic rings were suspended in organ chambers filled with physiological salt solution (95% O2, 5% CO2, 37 degrees C), and isometric tension was measured. In studies designed to assess the tone-related release of nitric oxide (NO) from phenylephrine-precontracted aortic rings, we found that vasoconstriction induced by L-NAME was greater in aortic rings from sham-ovariectomized SHR (SHAM SHR) than in those obtained from ovariectomized SHR (OVX SHR). Concentration-related relaxant responses to superoxide dismutase were significantly greater in the SHAM SHR than in the OVX SHR. In contrast, receptor-mediated release of NO was not altered by ovariectomy, as deduced from acetylcholine (ACh) concentration-responses curves. Responses to the exogenous NO donor sodium nitroprusside (SNP) were also identical in both ovariectomized and sham-ovariectomized groups, ruling out differences in smooth muscle reactivity to NO. These results show that NO release is impaired in OVX SHR, an animal model of simultaneous hypertension and menopause.
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PMID:Long-term effect of bilateral ovariectomy on endothelial function in aortic rings of spontaneously hypertensive rats: role of nitric oxide. 1137 13

This study investigated the influence of NO, potassium (K+) channel blockade, and the phosphodiesterase inhibitors (PDEIs) theophylline (non-selective PDEI), siguazodan (PDE3I), rolipram (PDE4I), and zaprinast (PDE5I) on rat isolated main pulmonary artery hypoxic (95% N2 and 5% CO2) vasoconstriction. Hypoxic vasoconstriction increased by 27% (p < 0.01) in the presence of the NO synthase inhibitor L-NAME (10(-4) M), and by 15% (p < 0.05) in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M), without potentiation by the combination of these two drugs. Hypoxic vasoconstriction decreased by 28% (p < 0.01) in presence of the Kv,-voltage-dependent channel blocker 4-aminopyridine (10(-3) M), whereas the other K+ channel blockers, charybdotoxin (BKCa, large-conductance Ca2+-sensitive K+ channels) and apamin (SKCa, small-conductance Ca2+-sensitive K+ channels) had no effect. The nonselective PDEI theophylline induced a concentration-dependent relaxation (pD2 = 4.05, Emax = 90% [expressed as a percentage of maximal relaxation induced by papaverine 10(-4) M]). Among the selective PDEIs, siguazodan was significantly (p < 0.01) more efficient than rolipram and zaprinast (Emax values were 84%, 67%, and 58%, respectively) and significantly (p < 0.05) more potent than zaprinast (pD2 values were 6.48, 6.34, and 6.16 for siguazodan, rolipram, and zaprinast). Glibenclamide and L-NAME significantly (p < 0.05) shifted the concentration-response curve (CRC) for zaprinast to the right, and L-NAME shifted the CRC significantly to the right for siguazodan. In the presence of L-NAME, glibenclamide had no effect on the CRC of zaprinast. We conclude that (a) NO exerts a permanent inhibitory effect against hypoxic vasoconstriction that might be mediated in part by an activation of K(ATP) channels; (b) a 4-aminopyridine-sensitive K+ channel is involved in vasoconstriction under hypoxic conditions; (c) PDEs 3 and 5 are the predominant PDE isoforms in rat pulmonary artery relaxation; and (d) NO and K(ATP), but neither BK(Ca), SK(Ca), nor Kv channels, are involved in the relaxant effect of PDEIs.
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PMID:Hypoxic vasoconstriction of rat main pulmonary artery: role of endogenous nitric oxide, potassium channels, and phosphodiesterase inhibition. 1148 82

The role of the L-arginine-nitric oxide (NO) system, the role of the endogenous morphine-like substances (endorphins), and the possible interaction between these two systems in the modulation of regional cerebral and spinal CO2 responsiveness was investigated in anesthetized, ventilated, normotensive, normoxic cats. Regional cerebral blood flow was measured with radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions in nine individual cerebral and spinal cord regions. General opiate receptor blockade by 1 mg/kg naloxone intravenously alone or NO synthase blockade by 3 mg/kg N(omega)-nitro-L-arginine-methyl ester (L-NAME) intravenously alone caused no changes in regional CO2 responsiveness. Combined administration of these two blocking agents in the very same doses, however, resulted in a strong potentiation, with a statistically significant reduction of the CO2 responsiveness observed. Separation of the blood flow response to hypercapnia and hypocapnia indicates that this reduction occurs only during hypercapnia. Specific mu and delta opiate receptors were blocked by 0.5 mg kg(-1) IV beta-funaltrexamine and 0.4 mg kg(-1) IV naltrindole, respectively. The role of specific mu and delta opiate receptors in the NO-opiate interaction was found to be negligible because neither mu nor delta receptor blockade along with simultaneous NO blockade were able to decrease CO2 responsiveness. The current findings suggest a previously unknown interaction between the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) system and the endogenous opiate system in the cerebrovascular bed during hypercapnic stimulation, with the phenomenon not mediated by mu or delta opiate receptors.
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PMID:Interactions between the endothelium-derived relaxing factor/nitric oxide system and the endogenous opiate system in the modulation of cerebral and spinal vascular CO2 responsiveness. 1148 29

During intestinal ischemia, CO2 accumulates in tissue as a result of bicarbonate buffering of anaerobic acid generation. Previous studies have shown that nitric oxide (NO) generated during ischemic preconditioning acts as a glycolytic modulator, thus decreasing tissue lactate production. We studied if ischemic preconditioning induces NO-dependent changes in static mesenteric venous blood Pco2 values and CO2 accumulation during intestinal ischemia. Superior mesenteric venous (smv) acid base variables were studied in 4 groups of rats: a control group (C), an ischemic (90-min period of flow arrest) group (I), an ischemic group subjected to previous ischemic preconditioning (P), and an ischemic group subjected to previous ischemic preconditioning in which nitric oxide synthase (NOS) was inhibited by N-nitro-L-arginine methyl ester (L-NAME) administration (P+N). Preconditioning induced acidosis in smv blood during reperfusion before ischemia, but this effect was counteracted by L-NAME. Group P showed the lowest values of end-ischemic tissue lactate, smv blood CO2 accumulation, and LDH in perfusate, whereas group P+N showed the highest level of LDH in perfusate but the lowest end-ischemic smv blood Pco2 and acidity. We conclude that lower ischemic CO2 accumulation in static smv blood, but not lower end-ischemic Pco2, was related with the protective effect of ischemic preconditioning in our rat model. Thus, the use of stagnant smv blood Pco2 as an indicative of intestinal dysoxia can lead to misinterpretations if a broader acid-base picture is not considered.
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PMID:CO2 in static mesenteric venous blood during intestinal ischemia and ischemic preconditioning in rats. 1169 82

In estrogen-depleted [i.e., ovariectomized (Ovx)] animals, an endothelium-derived hyperpolarizing factor (EDHF)-like mechanism may arise to, at least partially, replace endothelial nitric oxide (NO) synthase (eNOS)-derived NO in modulating cerebral arteriolar tone. Additional findings show that eNOS expression and function is restored in estrogen-treated Ovx female rats, while the nascent EDHF-like activity disappears. Because NO has been linked to repression of EDHF activity in the periphery, the current study was undertaken to examine whether the nascent EDHF role in cerebral vessels of Ovx females relates to a chronically repressed eNOS-derived NO-generating function. We compared the effects of chronic NOS inhibition with Nomega-nitro-L-arginine-methyl ester (L-NAME; 100 mg. kg-1. day-1 for 3 wk) on EDHF-mediated pial arteriolar vasodilation in anesthetized intact, Ovx, and 17beta-estradiol-treated (0.1 mg. kg-1. day-1 ip, 1 wk) Ovx (OVE) female rats as well as in male rats that were prepared with closed cranial windows. In the chronic NOS inhibition groups, pial arteriolar responses were monitored in the absence (all groups) and presence (females only) of indomethacin (Indo; 10 mg/kg iv). Finally, the gap junction inhibitory peptide Gap 27 (300 muM) was applied to block EDHF-related vasodilation. NO donor (S-nitroso-N-acetyl-penicillamine) responses were similar in all rats studied. Acetylcholine (ACh) reactivity was virtually absent in control Ovx rats and chronically NOS-inhibited intact female, OVE, and male rats. However, a partial recovery of ACh reactivity was seen in L-NAME-treated Ovx females. In addition, in the presence of L-NAME, a normal CO2 reactivity was observed in all females, whereas a 50% reduction in CO2 reactivity was seen in males. In intact and OVE rats, both chronic and acute (NG-nitro-L-arginine suffusion) NOS inhibition, combined with Indo, depressed ADP-induced dilation by > or =50%, and subsequent application of Gap 27 had no further effect on ADP-induced vasodilation. ADP reactivity was retained in Ovx rats after combined chronic NOS inhibition and acute Indo, but was attenuated significantly by Gap 27. In males, Gap 27 had no effect on arteriolar reactivity. Taken together, our data demonstrate that in the cerebral microcirculation, NO does not have an inhibitory effect on EDHF production or action. The increased EDHF-like function in chronic estrogen-depleted animals is not due to eNOS deficiency, suggesting a more direct effect of estrogen in modulating EDHF-mediated cerebral vasodilation.
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PMID:Nascent EDHF-mediated cerebral vasodilation in ovariectomized rats is not induced by eNOS dysfunction. 1286 71


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