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

We examined the role of acetylcholine and nitric oxide in the increases in cerebrocortical blood flow elicited by stimulation of a region of the basal forebrain from which the major cholinergic projection to the cerebral cortex originates. In halothane-anesthetized rats a 3 x 3 mm area of the parietal cortex was exposed and the site was superfused with Ringer (37 degrees C; pH 7.3-7). Cortical blood flow was monitored at the site of superfusion by laser-Doppler flowmetry. The basal forebrain was stimulated electrically (100 microA; 50 Hz) and stimulated sites were histologically verified at the end of the experiment. With Ringer superfusion (n = 8), basal forebrain stimulation increased neocortical flow by 185 +/- 9% (mean +/- S.E.M.). The flow increase was attenuated (-38 +/- 6%; n = 5) by superfusion with the muscarinic cholinergic antagonist atropine (100 microM). Superfusion with atropine plus the nicotinic antagonist mecamylamine (100 microM) did not attenuate the response further (P > 0.05 from atropine alone; n = 6). Superfusion with the nitric oxide synthase inhibitor nitro-L-arginine, but not with the inactive isomer nitro-D-arginine (n = 6), attenuated the vasodilation in a dose-dependent fashion (-43 +/- 4% at 1 mM; n = 7) and reduced nitric oxide synthase catalytic activity at the site of superfusion by 95 +/- 4%. Co-application of nitro-L-arginine and atropine did not attenuate the vasodilation further (P > 0.05 from nitro-L-arginine alone; n = 6). Administration of the somewhat selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (50 mg/kg, i.p.) attenuated the increases in flow produced by topical application of N-methyl-D-aspartate (40 microM; n = 5) or by hypercapnia (n = 7), but did not affect the vasodilation produced by basal forebrain stimulation (n = 5) and by topical application of acetylcholine (10 microM; n = 5). 7-nitroindazole reduced constitutive nitric oxide synthase enzymatic activity in forebrain by 72 +/- 3% (n = 8). The data suggest that the neocortical vasodilation elicited by basal forebrain stimulation is, in part, mediated by local release of acetylcholine which, in turn, leads to increased nitric oxide synthesis in endothelial cells.
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PMID:Role of nitric oxide and acetylcholine in neocortical hyperemia elicited by basal forebrain stimulation: evidence for an involvement of endothelial nitric oxide. 884 7

The pH has marked effects on the blood flow in several vascular beds but the underlying mechanisms remain incompletely understood. It is still not agreed, for example, whether it is the fall in extracellular pH or intracellular pH that is responsible for changes in tone resulting from hypercapnic acidosis. The issue has been further complicated by the recent discovery that nitric oxide (NO) may also be involved in vasodilator responses to hypercapnia with the result that, in some laboratories, attention has been focused away from vascular smooth muscle. The recent availability of fluorescent dyes sensitive to pH has enabled some of the uncertainties in this field to be addressed. In light of these new observations, we have attempted to put older viewpoints in perspective. We conclude that, whilst a fall in smooth muscle intracellular pH is likely to be responsible for immediate responses to acidosis, the extracellular pH probably plays the predominant role in the steady state. The role of NO is best investigated in the cerebral circulation where it plays an important modulating role in the response to acidosis, and is probably of extravascular origin.
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PMID:Effects of pH on vascular tension: which are the important mechanisms? 886 40

Since endothelium-dependent relaxation of cerebral vessels was first identified in 1980, the pivotal role of the endothelium has become evident not only in dilator responses but also in constrictor responses to various kinds of stimulation. Involvement of endothelium-derived relaxing factors (EDRFs) as well as endothelium-derived contracting factors (EDCFs) has been postulated in such vascular responses. In 1987, one of the EDRFs was determined to be nitric oxide (NO), a simple and very labile molecule, whereas endothelin composed of 21 amino acid residues was identified as one of the EDCFs in 1988. Since 1990, numerous studies which exclusively employed L-arginine analogues as specific NO synthase (NOS) inhibitors, have been undertaken to examine the role of NO in the regulation of the cerebral circulation. However, some conflicting data have emerged. The few points of consensus among the researchers may be summarized as follows: (1) NO, probably produced in the endothelium, plays an important role in the maintenance of the basal cerebral blood flow, (2) NO is not directly involved in hypoxic vasodilation, and (3) NO mediates a functional coupling of metabolism and cerebral blood flow in certain types of neural activation. Hypercapnic vasodilation and autoregulatory responses are still the main topics providing conflicting data with substantial areas of controversy. Besides ensuring appropriate experimental protocols, future studies require the precise monitoring of the degree and cellular specificity (endothelium, perivascular nerve fibers, neurons, etc.) of NOS inhibition in order to obtain concrete and reliable experimental data.
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PMID:Is nitric oxide really important for regulation of the cerebral circulation? Yes or no? 888 64

The effect of NG-nitro-L-arginine (L-NNA) on regional cerebral blood flow (rCBF) response to hypercapnia (5% CO2 inhalation) was studied in urethan-anesthetized wild-type (SV-129) and type III nitric oxide (NO) synthase (NOS)-deficient mice, using laser-Doppler flowmetry and the closed cranial window technique. Resting rCBF during normocapnia decreased by approximately 25% after L-NNA superfusion in wild-type mice only (n = 18), suggesting a role for type III NOS in baseline blood flow. Hypercapnia augmented rCBF approximately 50% in both wild-type and type III NOS mutant mice. L-NNA superfusion (1 mM) inhibited this increase by approximately 60% in both strains. Hence, synthesis of NO by the constitutively expressed type I NOS contributes to blood flow augmentation during hypercapnia.
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PMID:L-NNA-sensitive regional cerebral blood flow augmentation during hypercapnia in type III NOS mutant mice. 889 69

Inhibition of nitric oxide (NO) synthesis attenuates the hypercapnic cerebrovasodilation or the increases in cerebral blood flow (CBF) produced by acetylcholine (ACh), either topically applied or endogenously released in neocortex by stimulation of the basal forebrain cholinergic system. We investigated whether exogenous administration of NO, using NO donors, can reverse the attenuation of these responses by NO synthase (NOS) inhibitors. In halothane-anesthetized, ventilated rats the frontoparietal cortex was exposed and superfused with Ringer. CBF was monitored at the super fusion site by laser-Doppler flowmetry. The basal forebrain was stimulated (100 microA; 50 Hz) with microelectrodes stereotaxically implanted. Superfusion with the NOS inhibitor NG-nitro-L-arginine (L-NNA; 1 mM) reduced resting CBF (-38 +/- 2%; mean +/- SE) and attenuated the vasodilation elicited by hypercapnia (Pco2, 50-60 mmHg; -79 +/- 3%), ACh (10 microM; -83 +/- 7%), or basal forebrain stimulation (-44 +/- 2%) (P < 0.05, analysis of variance and Tukey's test). After L-NNA, topical application of 3-morpholinosydnonimine (SIN-1) (n = 7), S-nitroso-N-acetylpenicillamine (SNAP) (n = 6), or 8-bromoguanosine 3',5'-monophosphate (8-BrcGMP, n = 4) reestablished resting CBF (P > 0.05 from Ringer) and reversed the attenuation of the response to hypercapnia (P > 0.05 from Ringer). However, SIN-1 or SNAP failed to reverse the attenuation of the response to basal forebrain stimulation or topical ACh (P > 0.05 from L-NNA). After L-NNA, the NO-independent vasodilator papaverine (n = 4) reestablished resting CBF (P > 0.05 from Ringer) but failed to restore the hypercapnic vasodilation (P > 0.05 from L-NNA). The attenuation of hypercapnic response by the neuronal NOS inhibitor 7-nitroindazole was counteracted only partially by SIN-1 (n = 4) or 8-BrcGMP (n = 4). The data support the hypothesis that the vasodilation elicited by hypercapnia requires resting levels of NO for its expression, whereas the response to endogenous or exogenous ACh depends on agonist-induced NOS activation. In hypercapnia NO may act as a permissive factor by facilitating the action of other vasodilators, whereas in the vascular response initiated by ACh NO is likely to be the major mediator of smooth muscle relaxation.
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PMID:Permissive and obligatory roles of NO in cerebrovascular responses to hypercapnia and acetylcholine. 889 92

A number of innovative approaches have been explored in the hope of improving the outcome in newborns with congenital diaphragmatic hernia (CDH) and respiratory insufficiency. Among these are the techniques of delayed approach to the repair of the diaphragmatic hernia; permissive hypercapnia; nitric oxide and surfactant administration; intratracheal pulmonary ventilation; liquid ventilation; perfluorocarbon-induced lung growth; and lung transplantation. Although early in their clinical evolution, these interventions are developing rapidly and hold promise for improving the outcome in patients with CDH.
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PMID:Innovative therapies in the management of newborns with congenital diaphragmatic hernia. 893 55

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

Artificial ventilation plays a key role in the treatment of acute respiratory distress syndrome (ARDS). Initially, the goal is to normalize gas exchange compromised by the lung disease. Positive pressure ventilation can however aggravate prior lesions of the pulmonary parenchyma, at least in areas of the lung accessible to ventilation. Computed tomography of the lung has given us a better understanding of the pathogenesis of these ventilation-induced lesions, leading to new ventilatory strategies aimed at assuring adequate oxygenation without damaging the parenchyma. These ventilatory modes may tolerate a certain degree of hypercapnia to avoid lung injury. Improved oxygenation relies on optimizing the ventilation/perfusion ratio, either with inhaled nitric oxide or a supine position to improve alveolar recruitment. In the most severe cases, extra-corporal gas exchange systems have shown their efficacy for patients whose lungs cannot be ventilated. Thus ventilation should be carefully adapted to each patient based on the severity of the ARDS and its clinical course. We present a practical protocol based on a hierarchy rationale for each ventilation mode and indicate the explorations required to adapt each mode to a specific patient.
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PMID:[Artificial ventilation in acute respiratory distress syndrome in adults. Towards an individual optimization]. 895 78

We used the relatively selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (7-NI) to test the hypothesis that the increases in local cerebellar blood flow (BFcrb) elicited by activation of the cerebellar parallel fibers (PF) are mediated by neuronal production of nitric oxide. In halothane-anesthetized rats, the cerebellar cortex was exposed and superfused with Ringer solution (37 degrees C; pH 7.3-7.4). The PF were stimulated electrically (100 microA, 30 Hz, 40 s), while BFcrb was monitored at the site of stimulation by a laser-Doppler flow probe. In vehicle-treated rats (n = 5), PF stimulation increased BFcrb by 61 +/- 5% (P < 0.05; analysis of variance and Tukey's test). 7-NI attenuated the increase in BFcrb dose dependently (10-100 mg/kg i.p.; n = 5 animals/dose) and by 55 +/- 7% at 100 mg/kg (P < 0.05). The attenuation of the response to PF stimulation was correlated with the degree of inhibition of calcium-dependent brain nitric oxide synthase activity, measured ex vivo by the citrulline assay (n = 21). 7-NI also attenuated the cerebrovasodilation elicited by hypercapnia (PCO2 = 50-60 mmHg) but did not affect the vasodilation evoked by acetylcholine (10 microM; n = 4; P > 0.05; t-test), a response mediated by endothelial nitric oxide synthase. 7-NI did not attenuate the BFcrb increase evoked by the nitric oxide donor S-nitroso-N-acetylpenicillamine (1 mM; n = 5; P > 0.05; t-test). Similarly, 7-NI did not affect resting systemic arterial pressure. These observations suggest that selective inhibition of neuronal nitric oxide synthase by 7-NI attenuates the increases in BFcrb evoked by PF stimulation. The findings provide additional support to the hypothesis that the increase in BFcrb evoked by PF stimulation is mediated, in part, by glutamate-induced activation of neuronal nitric oxide synthase.
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PMID:7-Nitroindazole attenuates vasodilation from cerebellar parallel fiber stimulation but not acetylcholine. 896 22

Endogenous opioid peptides are present in cerebral perivascular nerves and in the CSF, and their concentrations are changing in response to stimuli that activate regulatory mechanisms of the cerebral circulation (e.g., alterations of the perfusion pressure or changes of the arterial O2 tension). Opiate receptors are expressed in the cells of the CNS and the cerebrovascular bed, and their activation modulates the function of other vasoregulatory mechanisms (i.e., the autonomic nervous system, nitric oxide, prostanoids, vasopressin) that are involved in the control of the cerebrovascular tone. The direct vasomotor effects of opioid peptides and opiates on the cerebral arteries under in vitro or in situ conditions appear to be weak or absent in several species. However, Met- and Leu-enkephalin induce pial arterial vasodilation in the newborn pig. In this species, beta-endorphin acts as a constrictor, whereas dynorphin may induce either dilation or constriction depending on the experimental conditions. The influence of exogenously applied natural and synthetic opioids on the cerebral blood flow (CBF) is determined mainly by their metabolic, neuronal, and respiratory effects. Hypothalamic and pituitary circulations are especially sensitive to opioids. Under resting conditions, endogenous opioid peptides do not participate in the regulation of the cerebrovascular tone and CBF. On the other hand, mu and delta opiate receptor stimulation by endogenous opioid peptides, interacting with other vasoactive factors, obviously contributes to the hypoxia- and hypercapnia-induced cerebral vasodilation. Furthermore, endogenous opioid mechanisms are involved in the autoregulation of the hypothalamic blood flow. Thus, the endogenous opioid system may well represent a latent regulatory mechanism, which is of limited importance under basal conditions, but becomes more important under conditions of stress. Synthetic exogenous opioids do not appear to influence the hypoxic or hypercapnic CBF responses or the cerebral autoregulatory process.
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PMID:Opiate receptor-mediated mechanisms in the regulation of cerebral blood flow. 896 68


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