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)

Changes in the rates of oxygen consumption and ammonium excretion, in intra- and extracellular acid-base status and in the rate of H+-equivalent ion transfer between animals and ambient water were measured during environmental hypercapnia in the peanut worm Sipunculus nudus. During exposure to 1 % CO2 in air, intracellular and coelomic plasma PCO2 values rose to levels above those expected from the increase in ambient CO2 tension. Simultaneously, coelomic plasma PO2 was reduced below control values. The rise in PCO2 also induced a fall in intra- and extracellular pH, but intracellular pH was rapidly and completely restored. This was achieved during the early period of hypercapnia at the expense of a non-respiratory increase in the extracellular acidosis. The pH of the extracellular space was only partially compensated (by 37 %) during long-term hypercapnia. The net release of basic equivalents under control conditions turned to a net release of protons to the ambient water before a net, albeit reduced, rate of base release was re-established after a new steady state had been achieved with respect to acid-base parameters. Hypercapnia also affected the mode and rate of metabolism. It caused the rate of oxygen consumption to fall, whereas the rate of ammonium excretion remained constant or even increased, reflecting a reduction of the O/N ratio in both cases. The transient intracellular acidosis preceded a depletion of the phosphagen phospho-l-arginine, an accumulation of free ADP and a decrease in the level of Gibbs free energy change of ATP hydrolysis, before replenishment of phosphagen and restoration of pHi and energy status occurred in parallel. In conclusion, long-term hypercapnia in vivo causes metabolic depression, a parallel shift in acid-base status and increased gas partial pressure gradients, which are related to a reduction in ventilatory activity. The steady-state rise in H+-equivalent ion transfer to the environment reflects an increased rate of production of protons by metabolism. This observation and the reduction of the O/N ratio suggest that a shift to protein/amino acid catabolism has taken place. Metabolic depression prevails, with completely compensated intracellular acidosis during long-term hypercapnia eliminating intracellular pH as a significant factor in the regulation of metabolic rate in vivo. Fluctuating levels of the phosphagen, of free ADP and in the ATP free energy change values independent of pH are interpreted as being correlated with oscillating ATP turnover rates during early hypercapnia and as reflecting a tight coupling of ATP turnover and energy status via the level of free ADP.
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PMID:Acid-base regulation, metabolism and energetics in sipunculus nudus as a function of ambient carbon dioxide level 939 Sep 35

It is well known that changes in PCO2 or PO2 strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 micrograms.kg-1.min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry Administration of L-NMMA reduced ocular fundus pulsation. (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia (PCO2 = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery (P < 0.05) and in the choroid (P < 0.05) was significantly blunted by L-NMMA. On the contrary, L-NMMA did not affect hyperoxia-induced (PO2 = 530 mmHg) hemodynamic changes. The hemodynamic effects of L-NMMA (at baseline and during hypercapnia) were reversed by coadministration of L-arginine. The present study supports the concept that NO has a role in hypercapnia induced vasodilation in humans.
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PMID:Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans. 943 55

To elucidate the differential reactivity of pulmonary microvessels in the acini to hypoxia, excessive CO2, and increased H+, we investigated changes in the diameter of precapillary arterioles, postcapillary venules, and capillaries in isolated rat lungs on exposure to normocapnic hypoxia (2% O2), normoxic hypercapnia (15% CO2), and isocapnic acidosis (0.01 mol/L HCl). Microvascular diameters were precisely examined using a real-time confocal laser scanning luminescence microscope coupled to a high-sensitivity camera with an image intensifier. Measurements were made under conditions with and without indomethacin or N(omega)-nitro-L-arginine methyl ester to assess the importance of vasoactive substances produced by cyclooxygenase (COX) or NO synthase (NOS) as it relates to the reactivity of pulmonary microvessels to physiological stimuli. We found that acute hypoxia contracted precapillary arterioles that had diameters of 20 to 30 microm but did not constrict postcapillary venules of similar size. COX- and NOS-related vasoactive substances did not modulate hypoxia-elicited arteriolar constriction. Hypercapnia induced a distinct venular dilatation closely associated with vasodilators produced by COX but not by NOS. Arterioles were appreciably constricted in isocapnic acidosis when NOS, but not COX, was suppressed, whereas venules showed no constrictive response even when both enzymes were inhibited. Capillaries were neither constricted nor dilated under any experimental conditions. These findings suggest that reactivity to hypoxia, CO2, and H+ is not qualitatively similar among intra-acinar microvessels, in which COX- and NOS-associated vasoactive substances function differently.
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PMID:Response of intra-acinar pulmonary microvessels to hypoxia, hypercapnic acidosis, and isocapnic acidosis. 954 81

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

Hypercapnia elicits hypothermia in a number of vertebrates, but the mechanisms involved are not well understood. In the present study, we assessed the participation of the nitric oxide (NO) pathway in hypercapnia-induced hypothermia and hyperventilation by means of NO synthase inhibition by using Nomega-nitro-L-arginine (L-NNA). Measurements of ventilation, body temperature, and oxygen consumption were performed in awake unrestrained rats before and after L-NNA injection (intraperitoneally) and L-NNA injection followed by hypercapnia (5% CO2). Control animals received saline injections. L-NNA altered the breathing pattern during the control situation but not during hypercapnia. A significant (P < 0.05) drop in body temperature was measured after both L-NNA (40 mg/kg) and 5% inspired CO2, with a drop in oxygen consumption in the first situation but not in the second. Hypercapnia had no effect on L-NNA-induced hypothermia. The ventilatory response to hypercapnia was not changed by L-NNA, even though L-NNA caused a drop in body temperature. The present data indicate that the two responses elicited by hypercapnia, i.e., hyperventilation and hypothermia, do not share NO as a common mediator. However, the L-arginine-NO pathway participates, although in an unrelated way, in respiratory function and thermoregulation.
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PMID:Effect of nitric oxide synthase inhibition on hypercapnia-induced hypothermia and hyperventilation. 972 71

1. We examined the vasodilatory effect of hypercapnia in the rat isolated mesenteric vascular bed. The preparation was perfused constantly (5 ml min(-1) with oxygenated Krebs-Ringer solution, and the perfusion pressure was measured. In order to keep the extracellular pH (pHe) constant (around 7.35) against a change in CO2, adequate amounts of NaHCO3 were added to Krebs-Ringer solution. 2. In the endothelium intact preparations, an increase in CO2 from 2.5% to 10% in increments of 2.5% decreased the 10 microM phenylephrine (PE)-produced increase in the perfusion pressure in a concentration-dependent manner. Denudation of the endothelium by CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate) (5 mg l(-1), 90 s perfusion) abolished the vasodilatory effect of hypercapnia. 3. An increase in CO2 from 5% to 10% reduced the increases in the perfusion pressure produced by 10 microM PE and 400 nM U-46619 by 48% and 44%, respectively. NG-monomethyl-L-arginine (100 microM) and indomethacin (10 microM) did not affect the vasodilatory effect of hypercapnia, whereas the vasodilatory response of the preparation to hypercapnia disappeared when the preparation was contracted by 60 mM K+ instead of PE or U-46619. 4. The vasodilatory effect of hypercapnia observed in the PE- or U-46619-precontracted preparation was affected by neither tetraethylammonium (1 mM), apamin (500 microM), glibenclamide (10 microM), nor 4-aminopyridine (1.5 mM). On the other hand, pretreatment with Ba2+ at a concentration of 0.3 mM abolished the hypercapnia-produced vasodilation. 5. An increase in the concentration of K+ in Krebs-Ringer solution from 4.5 mM to 12.5 mM in increments of 2 mM reduced the PE-produced increase in the perfusion pressure in a concentration-dependent manner. Pretreatment of the preparations with not only Ba2+ (0.3 mM) but also CHAPS abolished the vasodilatory effect of K+. 6. The results suggest that an increase in CO2 produces vasodilation by an endothelium-dependent mechanism in the rat mesenteric vascular bed. The membrane hyperpolarization of the endothelial cell by an activation of the inward rectifier K+ channel seems to be the mechanism underlying the hypercapnia-produced vasodilation. Neither nitric oxide nor prostaglandins are involved in this response.
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PMID:Involvement of barium-sensitive K+ channels in endothelium-dependent vasodilation produced by hypercapnia in rat mesenteric vascular beds. 977 57

Responses to hypercapnia and acetylcholine by newborn piglet pial arterioles are prostanoid dependent but appear to require both prostanoids and nitric oxide in juvenile pigs. We hypothesized that cerebrovascular dilatory responses become less prostanoid dependent and more NO dependent with development. Pial arteriolar responses to hypercapnia and histamine were recorded from alpha-chloralose-anesthetized newborn and juvenile pigs with closed cranial windows. Responses were recorded during control, after indomethacin or N(omega)-nitro-L-arginine (L-NNA), and after inhibitor plus iloprost or sodium nitroprusside. Indomethacin blocked newborn hypercapnic responses and markedly attenuated histamine dilations, but only reduced the dilations to about half in juveniles. Iloprost at subdilator concentrations restored newborn responses to hypercapnia and histamine but did not alter either response in indomethacin-treated juveniles. L-NNA attenuated juvenile, but not newborn, hypercapnia-induced dilations. Sodium nitroprusside did not restore the response. L-NNA did not alter responses to histamine in either age group. Cerebrovascular dilations to hypercapnia and histamine are prostanoid dependent and nitric oxide independent in the newborn pig, whereas nitric oxide assumes an increasing role in hypercapnic, but not histamine, responses with development.
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PMID:NO and prostanoids: age dependence of hypercapniaand histamine-induced dilations of pig pial arterioles. 1040 9

The issue of whether the acinar microvessel response to alveolar hypoxia and hypercapnia is impaired in injured lungs has not been vigorously addressed, despite the importance of knowing whether it is or not when treating patients with serious lung injury in terms of permissive hypercapnia. Applying a real-time laser confocal luminescence microscope, we studied hypoxia- and hypercapnia-induced changes in the diameter of the intra-acinar arterioles, venules, and capillaries of isolated rat lungs harvested from animals exposed for 48 h to 21% O(2) (group N) or 90% O(2) (group H). Measurements were made with and without inhibition of nitric oxide (NO) synthase (NOS) by N(omega)-nitro-L-arginine methyl ester or of cyclooxygenase (COX) by indomethacin at different basal vascular tones evoked by thromboxane A(2) (TXA(2)) analog. Hypoxia in the absence of TXA(2) contracted arterioles in group N but not in group H. Attenuated hypoxia-induced arteriole constriction was restored almost fully by inhibiting NOS and partially by inhibiting COX. Hypercapnia induced venule dilation in group N, but did not dilate venules in group H, irrespective of TXA(2). NOS inhibition in hypercapnia unexpectedly enhanced venule and arteriole dilation in group H. These responses no longer occurred when NOS and COX were inhibited simultaneously. In conclusion, microvessel reactions to hypoxia and hypercapnia are abnormal in hyperoxia-injured acini, in which NO directly attenuates hypoxia-induced arteriole constriction, whereas COX inhibited by excessive NO impedes hypercapnia-induced microvessel dilation.
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PMID:Nitric oxide differentially attenuates microvessel response to hypoxia and hypercapnia in injured lungs. 1040 72

In the newborn, cyclooxygenase (COX)-derived products play an important role in the cerebrovascular dysfunction after ischemia-reperfusion (I/R). We examined effects of I/R on expression of COX-1 and COX-2 isoforms in large cerebral arteries of anesthetized piglets. The circle of Willis, the basilar, and the middle cerebral arteries were collected from piglets at 0.5-12 h after global ischemia (2.5-10 min, n = 50), hypoxia (n = 3), or hypercapnia (n = 2) and from time-control (n = 19) or untreated animals (n = 7). Tissues were analyzed for COX-1 and COX-2 mRNA and protein using RNase protection assay and immunoblot analysis, respectively. Ischemia increased COX-2 mRNA by 30 min, and maximal levels were reached at 2 h. Hypoxia or hypercapnia had minimal effects on COX-2 mRNA. COX-2 protein levels were also consistently elevated by 8 h after I/R. Increases in COX-2 mRNA or protein were not influenced by pretreatment with either indomethacin (5 mg/kg iv, n = 5) or nitro-L-arginine methyl ester (15 mg/kg iv, n = 7). COX-1 mRNA levels were low in time controls, and ischemic stress had no significant effect on COX-1 expression. Thus ischemic stress leads to relatively rapid, selective induction of COX-2 in cerebral arteries.
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PMID:Ischemia-reperfusion rapidly increases COX-2 expression in piglet cerebral arteries. 1048 43

Isolated, cannulated, and pressurized (100 mmHg) middle cerebral arteries from adult cats were perfused intraluminally at rates from 0 to 4 ml/min with heated and gassed physiological saline solution. An electronic system held pressure constant by changing outflow resistance. The arteries constricted 18.1 +/- 0.95% in response to flow and depolarized from -54 +/- 0.51 to -40 +/- 1.26 mV (P < 0.05). Constriction was independent of a functional endothelium but was eliminated by superoxide dismutase or tyrosine kinase inhibitors. Luminal perfusion with a synthetic extracellular matrix Arg-Gly-ASP (RGD) peptide that binds with integrin significantly reduced constriction to flow. Neither reducing intraluminal pressure nor increasing tone or shear stresses altered constriction to flow. Flow-induced constriction did not impede the ability of the arteries to dilate to hypercapnia, and inhibiting flow-induced constriction did not alter contractile responses to other agonists. These data suggest that, in vitro, middle cerebral arteries constrict to flow through a mechanism involving free radicals and tyrosine kinase and that flow shear stresses resulting in constriction are transduced by integrin signaling.
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PMID:Integrin signaling, free radicals, and tyrosine kinase mediate flow constriction in isolated cerebral arteries. 1060 Aug 45

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