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)

The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/- 6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for at least 2 h. Raising PaCO2 from a control level of 40 to 68 mm Hg increased CBF to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. L-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. D-Arginine had no such effect. Decreasing PaCO2 to 20 mm Hg reduced control CBF to 46 +/- 3 ml 100 g-1 min-1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension. 140 Jun 48

The endothelium-derived relaxing factor (EDRF), probably nitric oxide (NO) or a closely related compound (EDRF/NO), is a potent vasodilator that appears to regulate vascular tone in several vascular beds. I have investigated whether EDRF/NO is also involved in the regulation of the cerebral circulation--in particular, whether EDRF/NO participates in the increases in cerebral blood flow elicited by hypercapnia. Rats were anesthetized with halothane, 1-2% (vol/vol), paralyzed, and artificially ventilated. Arterial pressure was monitored and blood gases were controlled. Cerebral blood flow was continuously monitored through a cranial window over the sensory cortex by a laser-Doppler probe. The window was superfused with Ringer's solution (pH 7.3-7.4 at 37 degrees C). During superfusion with Ringer's solution, hypercapnia (PCO2 = 55.8 +/- 0.8 mmHg) increased cerebral blood flow by 121 +/- 6% (n = 27; P less than 0.001; analysis of variance). Topical superfusion with the NO synthase inhibitors N omega-nitro-L-arginine (1 mM) attenuated the cerebrovasodilation by 93 +/- 6% (n = 8). In contrast, the vasodilation elicited by topical papaverine (1 mM) was not affected by N omega-nitro-L-arginine (n = 10). Application of N omega-nitro-D-arginine (1 mM) did not affect the cerebrovasodilation elicited by hypercapnia (P greater than 0.05; n = 8). N omega-Methyl-L-arginine (1 mM) attenuated the cerebrovasodilation elicited by hypercapnia by 44 +/- 4% (n = 8; P less than 0.001), an effect completely reversed by coapplication of L-arginine (10 mM; P greater than 0.05; n = 13). These findings indicate that the powerful effects of CO2 on the cerebral circulation are mediated by arginine-derived EDRF/NO. EDRF/NO is an important molecular signal whose actions may also include the regulation cerebral circulation.
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PMID:Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? 157 Mar 13

The effects of i.v. administration of a nitric oxide (NO) synthase inhibitor, L-NG-nitroarginine (L-NOArg), on the increase in cerebral cortical blood flow (cortical BF), following either electrical stimulation of the nucleus basalis of Meynert (NBM), whose cholinergic fibers project to the cortex, or hypercapnia with 10% CO2 inhalation, were studied in anesthetized rats. Cortical BF was measured using laser Doppler flowmetry. The threshold intensity of electrical stimulation of the NBM (0.5 ms, 50 Hz for 10 s) that induced an increase in regional cortical BF was defined as 1T. The cortical BF was increased on a stimulus intensity dependent manner at 1T-5T intensities tested. L-NOArg was administered cumulatively i.v. starting from 0.3 mg/kg, then 3 mg/kg, and 30 mg/kg. Time interval between each cumulative administration of L-NOArg was approximately 40 min. Three and 30 mg/kg of L-NOArg significant reduced the NBM stimulation-induced increase of cortical BF at intensities of 2T and 3T. The response at an intensity of 5T was reduced only by 30 mg/kg of L-NOArg to about half the control response. The reduced responses at 2T, 3T, and 5T were reversed following the i.v. administration of a physiological precursor of NO, L-arg (300 mg/kg). Inhalation of 10% CO2 for 15 s induced an increase in cortical BF which was not influenced by L-NOArg and L-Arg. These results suggest that NO is a necessary factor in the vasodilation of the cortical BF that is brought about by cholinergic fibers originating in the NBM.
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PMID:Nitric oxide (NO) is involved in increased cerebral cortical blood flow following stimulation of the nucleus basalis of Meynert in anesthetized rats. 160 50

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

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

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

It has discovered recently that nitric oxide (NO) is an important activating factor to blood vessels. Nitric oxide activates the soluble guanylate cyclase in the vascular smooth muscle. It is clear that nitric oxide does not act only on systemic blood vessels under physiological conditions. However, in hypoxia and hypercapnia, there are many controversies about the regulation of nitric oxide on cerebral blood vessels. In this paper, we have reviewed the latest advances in this field.
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PMID:[Regulation of nitric oxide on cerebral blood flow]. 760 20

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

The catastrophic pulmonary failure that complicates management of patients with multiple trauma or sepsis syndrome with shock is recognizable to nearly all experienced surgeons. However, the spectrum of injury is broad, the distribution of lung injury may be heterogeneous within a single patient, and many patients will not develop acute respiratory distress syndrome (ARDS) even after a major predisposing insult. The lung responds stereotypically to many disparate insults, so a better conceptual construct of ARDS may be to consider it as one component of the multiple organ dysfunction syndrome. Support of oxygen transport with positive pressure ventilation and high levels of positive end-expiratory pressure, long the mainstay of pulmonary support, has been criticized for its predilection to cause barotrauma. Newer modes of ventilation, such as pressure-controlled, inverse-ratio ventilation and permissive hypercapnia, are under investigation but have not yet been reported with scientific rigor. However, pulmonary support extends beyond the support of gas exchange. Fluid management requires close attention so that the circulation is supported but lung water accumulation is minimized. Nosocomial pneumonia greatly increases the mortality rate in ARDS, but is difficult to diagnose and must be sought aggressively. Until recently, pharmacologic therapy has held little promise, but inhalation of very low concentrations of nitric oxide appear to decrease pulmonary vascular pressures and intrapulmonary shunt. It remains unknown whether nitric oxide is effective therapy for the underlying injury, or is simply treatment for certain manifestations.
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PMID:Organ-specific support in multiple organ failure: pulmonary support. 767 4


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