Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the cerebellar parallel fibers (PF) releases glutamate and leads to depolarization of Purkinje cells and interneurons. These cells, in turn, release GABA. We have studied the role of glutamate, GABA, nitric oxide (NO) and adenosine in the increases in cerebellar cortex blood flow (BFcrb) elicited by PF stimulation. In anesthetized rats (halothane 1%) the cerebellar vermis was exposed and the site was superfused with Ringer (37 degrees C, pH 7.4). The PF were stimulated electrically (50-100 microA; 30 Hz) and the increases in BFcrb were recorded using a laser-Doppler flowmeter. Field potentials were recorded using glass microelectrodes. During Ringer superfusion, PF stimulation increased BFcrb by 58 +/- 5% (P < 0.001; analysis of variance; n = 6). Superfusion with the broad spectrum glutamate receptor antagonist kynurenic acid (Kyn; 5 mM) abolished the negative component of the field potential (n = 4), a finding reflecting lack of depolarization of Purkinje cells and interneurons, and blocked the increase in BFcrb (P > 0.05 from Ringer; n = 6). In contrast, Kyn did not influence the increase in BFcrb evoked by hypercapnia (pCO2 55.4 +/- 1.1 mmHg) or by superfusion with the NO donor SIN-1 (0.1, 1 mM; P > 0.05; n = 6). Superfusion with the adenosine receptor antagonist 8-sulphophenyltheophylline (8-SPT; 100 microM) reduced the elevation in BFcrb by 45 +/- 4% (P < 0.05; n = 6) and co-application of 8-SPT and of the NO synthase inhibitor nitro-L-arginine (L-NA; 1 mM) attenuated the vasodilation further (-82 +/- 4% from Ringer; P < 0.01 from 8-SPT alone).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex. 753 29

The relaxant effect of hypercapnia (15% CO2) was studied in isolated circular segments of rat basilar arteries with intact endothelium. The nitric oxide synthase inhibitor nitro-L-arginine (L-NOARG) and the cytosolic guanylate cyclase inhibitor methylene blue (MB), significantly reduced this relaxation by 54% and 70%, respectively. The effect of L-NOARG was completely reversed by L-arginine. Blockade of nerve excitation with tetrodotoxin (TTX) had no affect on the 15% CO2 elicited vasodilatation. Measurements of cGMP in vessel segments showed no significant increase in cGMP content in response to hypercapnia. L-NOARG and MB, but not TTX, significantly reduced the basal cGMP content in cerebral vessels. Adding 1.5% halothane to the incubation medium did not result in a significant increase in cGMP content. Lowering the pH by cumulative application of 0.12 M HCl resulted in relaxation identical to that obtained by lowering the pH with 15% CO2. In vessel segments in which the endothelium had been removed beforehand 15% CO2 induced relaxation that was not different from that seen in vessels with intact endothelium. L-NOARG had no affect in endothelium denuded vessels. The results suggest that high CO2 elicits vasodilatation of isolated rat basilar arteries by a mechanism independent of nitric oxide synthase (NOS) activity. The markedly reduced basal cGMP levels in cerebral vessels by L-NOARG and MB suggest that there exists a basal NO formation in the cerebral vessel wall.
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PMID:Hypercapnic vasodilatation in isolated rat basilar arteries is exerted via low pH and does not involve nitric oxide synthase stimulation or cyclic GMP production. 753 5

We investigated whether nitric oxide (NO) played a role in the generation of cerebrocortical flow oscillations and their modification by hypocapnia, hypercapnia, and halothane administration. Parietal cortical laser-Doppler flow (LDF) was monitored transcranially in anesthetized (barbiturate + 0-1.0% halothane), artificially ventilated, adult male Sprague-Dawley rats. Thirty minutes after infusion of N omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) mean arterial pressure (MAP) increased from 105 +/- 10 to 132 +/- 15 mmHg (P < 0.02), while mean LDF decreased from 159 +/- 36 to 135 +/- 30 perfusion units (PU, P < 0.05). Oscillations in LDF at a frequency of 6.3-7.8 cycles/min and amplitude of 10% were induced or augmented by L-NAME but not by D-NAME or indomethacin (2 mg/kg i.p.). L-arginine (200 mg/kg) abolished the oscillations post-L-NAME at constant MAP. Sodium nitroprusside infusion (10(-5) M, 5-50 microliters/min) reversed the L-NAME-induced increase in MAP and decrease in mean LDF but did not attenuate the flow oscillations. Hypocapnia post-L-NAME decreased LDF to 110 +/- 20 PU (P < 0.001) and augmented the flow oscillations (amplitude: 11-31%). Hypercapnia (5% CO2) or halothane (0.4-1.0%) suspended the oscillations in the presence of L-NAME. The results suggest that NO synthase activity inhibits cerebrocortical flow oscillations, and NO is not an obligatory mediator of the effects of halothane, hypocapnia, and hypercapnia on oscillatory activity.
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PMID:Modification of cerebral laser-Doppler flow oscillations by halothane, PCO2, and nitric oxide synthase blockade. 754 53

The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg-1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19-27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood-brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.
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PMID:The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats. 754 91

Isoflurane-anesthetized newborn pigs were used to test the hypothesis that nitric oxide mediates autoregulatory dilations of retinal arterioles. Fundus images were monitored by videomicroscopy at x310, and stimulus-induced changes in retinal arteriolar diameter were measured by on-line image analysis. Dilatative responses to systemic hypoxia (arterial O2 tension 20-30 mmHg), hypotension (mean arterial blood pressure 40 mmHg), or hypercapnia (arterial CO2 tension 70-85 mmHg) were assessed after intravitreal microsuffusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) over the observed arterioles. Twenty-five nanomoles L-NMMA constricted arterioles by 24 +/- 2% (P < 0.01; n = 17 pigs); a significant constriction (14 +/- 2%) was still observed 80 min after drug administration (n = 5). Complete nitric oxide synthase inhibition at this dose was indicated by the findings that co-administration of 2.5 mumol L-arginine reversed this constriction within 17 +/- 2 min (n = 3), that L-NMMA, but not D-NMMA, completely inhibited the 20 +/- 3% P < 0.01) arteriolar dilation induced by intravitreal acetylcholine (7.5 nmol; n = 4), and that no additional constriction was evidenced after administration of a 10-fold greater concentration of L-NMMA (n = 8). However, despite the prominent arteriolar constriction induced by L-NMMA under baseline conditions, increases in retinal arteriolar diameter still occurred in response to hypoxia (n = 5), hypotension (n = 4), or hypercapnia (n = 5) in animals pretreated with 50 nmol L-NMMA; these responses did not differ significantly from arteriolar dilations observed in untreated control animals (n = 16) subjected to the same stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide does not mediate autoregulation of retinal blood flow in newborn pig. 757 3

Sulfonylureas reduce cerebral blood flow (CBF) during hypoxia but not during hypercapnia, whereas blockers of nitric oxide (NO) synthesis reduce hypercapnic CBF. However, the effect of NO blockers on hypoxic CBF is uncertain. CBF was measured in the cortex of 51 enflurane-anesthetized rats by the hydrogen clearance technique during eucapnia, hypercapnia (arterial PCO2 65 Torr), and hypoxia (arterial PO2 40 Torr). CBF increased twofold in both hypercapnia and hypoxia from eucapnia. Intracortical (ic) NG-monomethyl-L-arginine (L-NMMA, 100 microM-5 mM) attenuated both the hypercapnic and hypoxic dilations by 60-70%, and L-arginine (300 mg/kg iv) partially reversed these effects. Glibenclamide (10 microM ic) and L-NMMA gave no further attenuation of the hypoxic dilation than L-NMMA alone. Cromakalim (10 microM, ic) increased CBF in eucapnia, but this was not seen in the presence of glibenclamide. The adenosine antagonist 8-phenyl-theophylline did not attenuate the hypoxic dilation. This suggests that NO synthesis plays a major role in the regulation of CBF in hypercapnia and hypoxia. But the combined effects of glibenclamide and L-NMMA do not further attenuate CBF in hypoxia.
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PMID:Effect of L-NMMA, cromakalim, and glibenclamide on cerebral blood flow in hypercapnia and hypoxia. 757 35

Nerve cells release nitric oxide (NO) in response to activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. We explored the hypothesis that NO influences the changes of cerebral blood flow (CBF) during cortical spreading depression (CSD), which is known to be associated with NMDA receptor activation. CBF was monitored in parietal cortex by laser-Doppler flowmetry in halothane-anesthetized rats. Under control conditions, CSD induced regular changes of CBF, which consisted of four phases: a brief hypoperfusion before the direct current (DC) shift; a marked CBF rise during the DC shift; followed by a smaller, but protracted increase of CBF; and a prolonged CBF reduction (the oligemia). NO synthase inhibition by intravenous and/or topical application of NG-nitro-L-arginine enhanced the brief initial hypoperfusion, but the CBF increases and the oligemia were unchanged. L-Arginine prevented the development of the prolonged oligemia after CSD but had no influence on the marked rise of CBF during CSD. Animals treated with L-arginine recovered the reduced vascular reactivity to hypercapnia after CSD much faster than control rats. Functional denervation of cortical and pial arterioles by tetrodotoxin accentuated the pre-CSD hypoperfusion and the oligemia but did not affect the CBF increases. The results suggest that NO is important for the changes of cerebrovascular regulation following CSD. The observations may have clinical importance, since CBF changes during migraine may be triggered by CSD.
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PMID:Arginine-nitric oxide pathway and cerebrovascular regulation in cortical spreading depression. 763 52

We studied whether the increases in cortical cerebral blood flow (CBF) elicited by stimulation of the cerebellar fastigial nucleus (FN) are attenuated by systemic administration of inhibitors of nitric oxide synthase (NOS) and, if so, whether NOS-containing perivascular nerves arising from the sphenopalatine ganglia (SPG) are the source of NO during FN stimulation. Rats were anesthetized (1-3% halothane) and artificially ventilated. The FN or the pontine reticular formation (PRF) was stimulated electrically through a stereotaxically implanted microelectrode. To eliminate the elevation in arterial pressure (AP) elicited by FN or PRF stimulation the cervical spinal cord was transected and AP was maintained by intravenous phenylephrine. CBF was measured by a laser-Doppler probe placed over the parietal cortex. Systemic administration of the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 5-40 mg/kg) reduced resting CBF, an effect that was maximal at 10 mg/kg (-30 +/- 4%; n = 6; P < 0.003, analysis of variance). L-NAME, but not its inactive isomer D-NAME, attenuated the increases in CBF elicited by FN stimulation or hypercapnia in a dose-dependent fashion (10-40 mg/kg). At 40 mg/kg, the response to FN stimulation was reduced by 80 +/- 6% (n = 6; P < 0.05) and that to hypercapnia was reduced by 70 +/- 9% (P < 0.05). In contrast, the increases in CBF elicited by PRF stimulation were not affected (10-40 mg/kg; P > 0.05; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of nitric oxide synthase-containing vascular nerves in cerebrovasodilation elicited from cerebellum. 768 93

Hypercapnia induces initial constriction and prolonged relaxation of rat small mesenteric arteries. The mechanism of the relaxation is unknown, but has been attributed to lowering of pHi in the vascular smooth muscle. In this study we have investigated the response to raised PCO2 at constant pHo, in mesenteric small arteries precontracted with noradrenaline. 10% CO2 led to a fall in pHi associated with acute potentiation of tension, and subsequent relaxation. The relaxation did not occur in arteries in which the endothelium had been removed, nor in arteries pretreated with the nitric oxide synthase inhibitor, L-NAME (10(-4)M, NG-nitro-L-arginine methyl ester). The D-enantiomer, D-NAME, was without effect. We conclude that hypercapnic-induced vasodilatation in this circulation occurs via endothelium derived nitric oxide production.
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PMID:Carbon dioxide induced vasorelaxation in rat mesenteric small arteries precontracted with noradrenaline is endothelium dependent and mediated by nitric oxide. 768 47

Nitric oxide (NO) has recently been suggested to play a major role in a number of circulatory responses both within and outside the central nervous system. It has been linked to hypercapnic vasodilatation, metabolically driven changes in cerebral blood flow and hypoxia-induced changes in brain blood flow. In the studies the question of role of NO in hypercapnic vasodilatation and metabolically driven changes in flow is examined in the cat. Animals were anaesthetised with halothane and alpha-chloralose and ventilated. Cardiorespiratory parameters were monitored and kept within normal limits. Cerebral blood flow was monitored with laser Doppler flowmetry (CBFLDF) in the parietal cortex which metabolic activity was contemporaneously and continuously monitored using electrophysiological techniques. Hypercapnia was induced by increasing the end-expiratory CO2 to 8.1 +/- 0.4% and this produced a brisk rise in CBFLDF of 153 +/- 23%. Metabolic activity was increased by superfusion of the cortical surface with bicuculline (10 pmol) which increased cell firing and CBFLDF. Local administration of NG-nitro-L-arginine methyl ester (L-NAME) did affect the metabolically driven change in CBFLDF and only attenuated by 20% overall the hypercapnic vasodilator response. These studies suggest that at least in the anaesthetised cat NO does not play the pivotal role in these important vasodilator functions.
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PMID:Nitric oxide is not the sole determinant of hypercapnic or metabolically driven vasodilation in the cerebral circulation. 783 90


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