UMLS:C0020440 - FACTA Search

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Query: UMLS:C0020440 (hypercapnia)
7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nitric oxide (NO) synthesis in the cerebral hyperemic responses to hypercapnia and hypoxia was investigated in anesthetized rats. Regional CBF (rCBF) measurements were obtained in the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) using radiolabeled microspheres. The rCBF responses to either hypercapnia (PaCO2 = 70-80 mm Hg) or hypoxia (PaO2 = 40-45 mm Hg) were compared in rat groups studied in the presence and absence of NO synthase inhibition induced via the intravenous infusion of nitro-L-arginine methyl ester (L-NAME, 3 mg kg-1 min-1). Administration of L-NAME under normocapnic/normoxic conditions produced a 40-60% reduction in baseline rCBF values, indicating the presence of a NO "tone" in the cerebral vasculature. Infusion of L-NAME resulted in a substantial attenuation, in all regions measured, of the rCBF increases that normally accompany hypercapnia. In comparing saline-infused to L-NAME-infused rats, the percentage increases in rCBF (from normocapnic baseline values) were 351% versus 166% (CX), 446% versus 199% (SC), 443% versus 206% (BS), and 483% versus 174% (CE), respectively. The rCBF changes from baseline (delta rCBF in ml 100 g-1 min-1) were 488 versus 57 (CX), 570 versus 60 (SC), 434 versus 72 (BS), and 393 versus 45 (CE), respectively. These differences were all statistically significant (p < 0.05). During hypoxia, when compared to rats not given L-NAME, inhibition of NO synthase activity resulted in significantly greater (p < 0.05) percentage increases in rCBF (from normoxic baseline values) in most regions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide synthesis and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat. 841 12

1. The aims of this study were to compare in the rat isolated perfused lung preparation, the dilator actions of nicorandil, pinacidil and nitroglycerin on the hypoxic pulmonary pressure response with or without hypercapnic acidosis and to investigate the possible involvement of K channels and EDRF in these effects. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21%O2 + 5%CO2 + 74%N2 (normoxia) or 5%CO2 + 95%N2 (hypoxia) and perfused with a salt solution supplemented with ficoll and gassed with 40%CO2 + 60%N2 to produce hypercapnic acidosis. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and methylene blue (30 microM) were used to block KATP channels, KCa channels, EDRF synthesis and guanylate cyclase, respectively. 3. Hypoxic pressure response was significantly increased by hypercapnic acidosis (+115%, P < 0.001), L-NAME (+111%, P < 0.001), methylene blue (+100%, P < 0.05) but not by glibenclamide or charybdotoxin. In contrast none of these inhibitors affected the hypoxic hypercapnic acidosis response. 4. Nicorandil, pinacidil and nitroglycerin caused relaxation during the hypoxic pressure response and hypoxic hypercapnic acidosis response. Nicorandil was more potent in the latter. Glibenclamide inhibited the relaxant effects of nicorandil and pinacidil but not those of nitroglycerin during hypoxia alone. In contrast, glibenclamide inhibited the relaxant effects of the three drugs during hypoxia + hypercapnia. Charybdotoxin inhibited the relaxant effect of pinacidil during normocapnia and hypoxia but not those of nicorandil or nitroglycerin. Methylene blue inhibited partially the dilator response to pinacidil but did not modify the effects of nitroglycerin or nicorandil. 5. It is concluded that in the rat isolated lung preparation, EDRF limits hypoxic pulmonary vasoconstriction but not hypoxic vasoconstriction potentiated by hypercapnic acidosis, whereas KATP or KCa channels are not involved in either case. Nicorandil and pinacidil dilate pulmonary vessels mainly through KATP channels but the effects of pinacidil may also involve an additional mechanism of action through KCa channels. Finally it is suggested that nitroglycerin may partly exert its relaxant effects through KATP channels.
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PMID:Comparison of the effects of nicorandil, pinacidil and nitroglycerin on hypoxic and hypercapnic pulmonary vasoconstriction in the isolated perfused lung of rat. 864 7

In this study, we tested the hypothesis that nitric oxide (NO) and adenosine (ADO) are the principal mediators of severe hypoxia-induced vasodilation. In addition, we examined whether activation of N-methyl-D-aspartate (NMDA) receptors and/or perivascular nerves plays a role. A closed cranial window and intravital microscopy system was used to monitor diameter changes in pial arterioles (approximately 40 microns) in anesthetized rats. The relative contributions of ADO, NMDA, NO, and neuronal activation to hypoxic cerebrovasodilation were assessed using the blockers 8-sulfophenyltheophylline (8-SPT), MK-801, nitro-L-arginine methylester (L-NAME), and tetrodotoxin (TTX). Two experimental series were studied. In the first, we tested the effects of NOS inhibition, via topical L-NAME (1 mM), on moderate (PaO2 approximately 46 mmHg) then severe (PaO2 approximately 34 mmHg) hypoxia-induced dilation. To confirm that L-NAME was affecting specifically NO-dependent responses, we also examined, in each experiment, the vasodilatory responses to topical applications of NOS-dependent (adenosine diphosphate (ADP); acetylcholine (ACh)) and -independent (sodium nitroprusside (SNP)) agents, in the presence of L-NAME or, in controls, the presence of D-NAME or no added analogue. In the second series, topical suffusions of ADP, ADO, and NMDA were sequentially applied, followed by 5 min exposure to severe hypoxia (PaO2 approximately 32 mmHg). Following return to normoxia, a suffusion of either 8-SPT (10 microM), MK-801 (10 microM), TTX (1 microM), or 8-SPT+MK-801 was initiated (or, in controls, application of a drug-free suffusate was maintained), and the above sequence repeated. In control, TTX, and 8-SPT+MK-801 experiments, baseline conditions were then restored and hypercapnia (PaCO2 = 70-85 mmHg) was imposed. In the series 1 control groups, moderate and severe hypoxia elicited approximately 20% and 35-40% increases in diameter, respectively. L-NAME attenuated ADP- and ACh-induced dilations, did not alter the arteriolar responses to SNP or moderate hypoxia, but prevented further dilation upon imposition of severe hypoxia. This suggested that 45-50% of the severe hypoxia response was NO-dependent. In series 2, 8-SPT blocked the adenosine response and reduced severe hypoxia-induced dilation by 46%. MK-801 predictably blocked NMDA-induced relaxation and reduced the hypoxic response by 42%. When combined, 8-SPT and MK-801 affected hypoxic vasodilation additively. After TTX, the ADP and ADO responses were normal, but NMDA and hypoxia responses were completely blocked. Hypercapnia-induced dilation was unaffected by TTX or 8-SPT+MK-801. The results imply that severe hypoxia-induced release of NO and ADO, and the accompanying pial arteriolar dilation, are wholly dependent on the capacity to generate action potentials in perivascular nerves. The similarity of the L-NAME and MK-801 effects on hypoxic cerebrovasodilation suggests that the NO-dependency, to a large degree, derives from NMDA receptor activation.
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PMID:Role of nitric oxide, adenosine, N-methyl-D-aspartate receptors, and neuronal activation in hypoxia-induced pial arteriolar dilation in rats. 875 Sep 62

Nitric oxide synthase (NOS) blockade was used to test the cardioventilatory responses to hypercapnia and hypoxia in freely behaving animals. Chronically instrumented adult Sprague-Dawley rats were studied before and after intravenous administration of either 100 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS blocker, or 10 mg/kg of S-methyl-L-thiocitrulline (SMTC), a selective neural NOS inhibitor. L-NAME injection induced sustained blood pressure (BP) elevation with transient tachycardia and increased minute ventilation (VE), which returned to baseline within minutes. SMTC elicited similar, although transient, BP increases; however, heart rate and VE decreased. L-NAME and SMTC did not modify overall steady-state hypercapnic responses. In control conditions, hypoxia induced early VE increases with further VE enhancements at 30 min. L-NAME increased the early VE response to 10% O2 but induced late VE reductions in hypoxia. SMTC did not change early VE responses but induced marked reductions in the later VE hypoxic responses. In control animals, hypoxia induced a significant heart rate increase. This increase was absent during the early response after SMTC and was followed in both L-NAME- and SMTC-treated animals by significant heart rate reductions to values below room air. Similarly, the sustained BP response to hypoxia in control animals was absent after administration of NOS inhibitors. These findings suggest that NOS activity exerts excitatory influences on respiration and cardiac chronotropy and sustained vasomotor tone during hypoxia. We speculate that NOS-mediated mechanisms may play an important role in hypoxia-induced ventilatory roll-off during wakefulness.
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PMID:Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat. 894 31

Laser Doppler flowmetry was used to further investigate the role of nitric oxide (NO) in CO2-induced cerebrocortical hyperemia in rats. A second objective was to elucidate the source(s) of the NO involved in the response to hypercapnia. We used the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase (NOS) and 7-nitroindazole (7-NI) to selectively inhibit brain or nonendothelial NOS. Rats were anesthetized with a single dose of intraperitoneal (IP) pentobarbital (65 mg/kg) for surgery; 60-90 min later they were ventilated with 1.0% halothane in 30% O2 for 1 h to achieve a steady state. The animals were assigned to one of five groups. A control group (n = 9) was infused with 1 mL of saline. The second group (n = 10) received 20 mg/kg of L-NAME intravenously (IV). A third group (n = 9) also received L-NAME; in addition, cerebrocortical laser Doppler flow (LDF) and mean arterial pressure (MAP) were restored to baseline using the NO donor sodium nitroprusside (SNP). In a fourth group (n = 9), MAP was increased to the level usually seen after L-NAME with an infusion of phenylephrine (0.5-5 micrograms.kg-1.min-1). A fifth group (n = 11) received 7-NI at 40 mg/kg IP. The hypercapnic response of LDF was tested in all groups by adding 5% CO2 to the inspired gas at 30-45 min posttreatment; all changes in LDF were significant. In the control group, hypercapnia induced a 70% +/- 24% increase in LDF. In the L-NAME-treated group, the response was decreased to 36% +/- 22% at a posttreatment LDF that was 25% +/- 13% lower than the pre-L-NAME level. In the group where baseline LDF and MAP were restored with SNP, the CO2 response was 56% +/- 15% (not significant versus control). In the group in which MAP was increased with phenylephrine, the response to hypercapnia was 48% +/- 22% at a posttreatment LDF unchanged from pretreatment. These data suggest that increased vascular tone or the absence of basal NO after NOS inhibition influenced the vasodilator response to hypercapnia. In the 7-NI-treated group the response to hypercapnia was 38% +/- 3%, significantly attenuated at a posttreatment flow only 14% +/- 7% lower than pre-7-NI. We conclude that 1) endothelial NO does not mediate the response to hypercapnia but may have a permissive role in the response and 2) that brain NO may have an important role in response to hypercapnia.
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PMID:The role of nitric oxide in the cerebrovascular response to hypercapnia. 902 30

The roles of nitric oxide, adenosine and cortical arousal in the response to 7.5% CO2 inhalation were investigated by measuring cerebral blood flow bilaterally in the rat somatosensory cortices with laser-Doppler flow probes. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, i.v.) significantly attenuated the response to hypercapnia (mean decrease of 47%). This effect was partially reversed by a subsequent administration of L-arginine. Caffeine (10 mg/kg, i.v.) also significantly reduced hypercapnic responses (mean decrease of 44%). Caffeine administration was also associated with a tendency for animals to exhibit electrocorticographic signs of arousal; often associated with a reduction in the attenuation of the flow response to CO2 inhalation. 8-(3-Chlorostyryl) caffeine (CSC, 1.0 mg/kg), a selective antagonist at adenosine A2a striatal receptors failed to attenuate CO2-evoked responses, whereas CGS 15943, a less selective A2a receptor antagonist, significantly reduced CO2 responses. These data from the rat suggest (1) that both nitric oxide and adenosine may contribute to pial arteriolar vasodilatation during hypercapnia, and (2) that CO2 inhalation acts as a potent stimulus for cortical arousal, with enhanced neuronal activity contributing to the vascular response. The effects of administration of adenosine antagonists, such as the methylxanthines antagonists caffeine and theophylline, on CBF responses to hypercapnia can potentially be negated by the ability of these agents to facilitate CO2-induced cortical arousal.
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PMID:Hypercapnia-induced increases in cerebral blood flow: roles of adenosine, nitric oxide and cortical arousal. 920 26

Nitric oxide (NO) is a novel neurotransmitter candidate to which a large number of physiological roles has been ascribed. In the present study, immunocytochemistry was used to demonstrate NO synthase (NOS) and to investigate possible co-localization with other neurotransmitters. In the trigeminal ganglion of the cat, a moderate number of NOS immunoreactive nerve cell bodies was seen, of which the major part also expressed calcitonin gene-related peptide (CGRP). The nerve cell bodies expressing NOS in the trigeminal ganglion were predominantly of small to medium size; while numerous cell bodies of varying size contained CGRP. With in situ hybridization using oligonucleotide probes, CGRP mRNA was demonstrated in almost all trigeminal neurons of the cat. Stimulation of the nasociliary nerve resulted in a frequency-dependent increase in ipsilateral local cortical blood flow by 30 +/- 6%. Administration of the NOS inhibitor NG-nitro-L-arginine-methylester (L-NAME) did not significantly alter this response when applied intravenously or on the cortical surface. Local cortical administration of the CGRP blocker h-CGRP (8-37) did not alter the cerebral vasodilator response to hypercapnia or resting flow. However, the nasociliary nerve response was reduced by 50% after h-CGRP (8-37), with a general shift to the right of the frequency-response curve. These data suggest that although NOS is seen in several trigeminal ganglion cells and coexists with CGRP in a subpopulation of the sensory neurons, its role in trigeminally mediated vasodilatation was not significant.
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PMID:Calcitonin gene-related peptide and nitric oxide in the trigeminal ganglion: cerebral vasodilatation from trigeminal nerve stimulation involves mainly calcitonin gene-related peptide. 968 99

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

It has been demonstrated previously that isohydric hypercapnia (IH) does not affect agonist-induced tension development in pulmonary arteries. The aim of the present study was to examine the effects of IH on depolarisation-induced, steady state tension in the isolated rat pulmonary artery. Rings were submaximally contracted with high KCl under control conditions (5% CO(2)-95% air). IH was achieved by switching to a modified PSS (isosmotic substitution of NaHCO(3) for NaCl), equilibrated with 10% CO(2) in air. On switching to IH, a significant increase in mean (+/-SEM) tension (25.3+/-6.3% Tmax) was observed in endothelium intact rings (n=6). Endothelial removal significantly reduced this response. Non-specific inhibition of nitric oxide synthase (NOS) isoenzymes (L-NAME, 10(-3) M) abolished the IH-induced increase in tension while inhibition of neuronal NOS (TRIM, 10(-5) M) was without effect. The relaxant response to the nitric oxide donor sodium nitroprusside was similar in IH and control conditions. These results suggest that IH caused an endothelium-dependent increase in depolarisation-induced tension by reducing NO production.
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PMID:Hypercapnia-induced contraction in isolated pulmonary arteries is endothelium-dependent. 1085 24

Intracerebral nitric oxide (NO) concentration was measured to establish the technique and to investigate the response of the NO concentration to CO(2)variations, hypoxia, and reduced cerebral perfusion pressure. An intracerebral nitric oxide sensor was used in 10 pigs. Cerebral microcirculation was measured by laser Doppler flowmetry. Five pigs received 40 mg/kg nitro-1-arginine methyl ester (L-NAME). Baseline NO concentration was 246 +/- 42 nM. Hypercapnia increased cerebral microcirculation (P< 0.05) and NO concentration (P< 0.05). Hypoxia decreased NO concentration (P< 0.05). During high intracranial pressure, cerebral microcirculation decreased (P< 0.05) before the NO concentration decreased (P< 0.05), and after normalisation of the intracranial pressure the NO concentration increased, but more slowly than the cerebral microcirculation. L-NAME caused a decrease in cerebral microcirculation (P< 0.05) and NO concentration (P< 0.05) to a new steady state, and L-NAME attenuated the changes in NO concentration after hypoxia (P< 0.05) and high intracranial pressure (P< 0.05). In conclusion, the electrochemical sensor appears to reliably detect changes in localised intracerebral NO concentration and seems to be a promising tool for direct measurement of this chemically unstable substance.
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PMID:Cerebral nitric oxide concentration and microcirculation during hypercapnia, hypoxia, and high intracranial pressure in pigs. 1102 35

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