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

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.
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PMID:Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postischemic hypoperfusion. 170 54

The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by the solitary neuroendocrine cells and the neuroepithelial bodies (NEBs). Immunohistochemically, neuron-specific enolase, serotonin, bombesin, and calcitonin are demonstrable in both components, whereas leu-enkephalin is demonstrable only in solitary NE cells. The precise function of and interplay between these two components under physiologic and pathologic conditions are not entirely clear. Current indications are that NEBs act as intrapulmonary chemoreceptors sensitive to hypoxia and hypercapnia, whereas solitary NE cells may have a paracrine, regulatory function. Even less clear is the possible role of solitary NE cells and NEBs in the processes associated with intrauterine and neonatal pulmonary growth and maturation. Various experimental manipulations have resulted in proliferation of solitary NE cells and NEBs. Of particular interest is the apparently selective proliferative effect on NEBs shown by several nitroso compounds. Diethylnitrosamine administration to hamsters for several weeks results in an increase in the number of NEBs and an increase in the number of cells per NEB. These hyperplastic NEBs express the same immunoreactive hormones as their normal counterparts. However, when NEB cells from diethylnitrosamine-treated hamsters are cultured in vitro a notable proportion of the resulting endocrine cells express ACTH immunoreactivity. Interestingly, the neoplasms that eventually develop in these hamsters are not comprised of NE cells. Studies on human bronchi from specimens resected for various types of neoplasms and for bronchiectasis with and without associated chronic obstructive pulmonary disease have revealed frequent hyperplasias of solitary NE cells and NEBs. In about 10% of the specimens, dysplastic aggregates of solitary NE cells and NEBs are found. Unexpected "microcarcinoids" and tumorlets are also seen. The mildly and moderately hyperplastic solitary NE cells and NEBs tend to express the hormones indigenous to the bronchi, whereas in the severely hyperplastic and dysplastic cells, "ectopic" hormones may also be expressed; the latter include predominantly ACTH and vasoactive intestinal polypeptide. A distinct hyperplasia of NEBs has been found in the lungs from individuals living at altitudes ranging from 3400 to 4300 meters; these changes may represent an adaptive response to chronic hypoxia parallel to the hyperplastic carotid paraganglia that may be found in the same type of population. Bronchopulmonary NE neoplasms comprise a spectrum that includes typical carcinoids, well-differentiated NE carcinomas, and NE carcinomas of intermediate and small cell types. Typical carcinoids are predominantly central, display little if any pleomorphism, are richly granulated by electron microscopy, and by immunohistochemistry express predominantly, although not exclusively, hormones indigenous to their site of origin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms. 613 58

Calcitonin and acetazolamide inhibit bone resorption in the ureter-ligated rat. Calcitonin treatment results in an ensuing hypocalcemia and hypophosphatemia. Although acetazolamide treatment results in a hypocalcemic response similar to that seen with calcitonin, plasma phosphate concentrations increase or remain unchanged after drug treatment. Data are presented indicating that acetazolamide exhibits two effects that influence blood phosphate. Drug treatment of ureter-ligated rats results in an inhibition of bone resorption which tends to lower blood phosphate concentrations. However, this effect is masked by a drug-induced hypercapnia which results in an increase in plasma phosphate concentrations. Elevation of blood pCO2 also attenuates the hypophosphatemic response to calcitonin.
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PMID:Sulfonamide inhibition of bone resorption: lack of a hypophosphatemia. 678 33

We examined the role of calcitonin gene-related peptide (CGRP) in cortical spreading depression (CSD)-induced dilation of rabbit pial arterioles. In urethan-anesthetized rabbits instrumented with a closed cranial window, CSD induction with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (mean +/- SE, n = 6) microns (a 54 +/- 9% increase). Topical administration of 12.8 microM CGRP-(8-37), a competitive inhibitor of the CGRP receptor, reduced CSD-induced pial dilation from 54 +/- 9% baseline to 33 +/- 9% (P < 0.05). Removal of the receptor antagonist from the brain surface restored CSD-induced dilation to 59 +/- 11% (P < 0.05, compared with the response with the antagonist present). In other animals, we showed that this dose of the CGRP antagonist attenuated arteriolar dilation to topically applied 10(-7) M CGRP (n = 5), but it did not alter arteriolar dilation to arterial hypercapnia. We also evaluated the dilator potency of substance P (SP) compared with CGRP. Dilation with 10(-7) M SP was only 22 +/- 11%, whereas arterioles dilated to 57 +/- 7% above baseline diameter with 10(-7) M CGRP. We conclude that CGRP contributes to the transient arteriolar dilation that is characteristic of CSD.
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PMID:Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits. 751 95

Concentrations of H+ and HCO3- rise in fluid lining hypercapnic airways. Effects of these ions on pulmonary endocrine cells were studied in 119 fetal rat lung organ cultures by semiquantitative staining for calcitonin gene-related peptide (CGRP)-like immunoreactive material. Intracellular CGRP was determined in cultures under "no-release" baseline conditions and after incubation in control or test media. After exposure to HCO3(-)-free medium at pH 7.4 (incubation control), CGRP fell moderately from no-release levels. Bombesin (1 ng/ml) promoted further significant loss of peptide, which was dependent on extracellular Ca2+ and inhibited by somatostatin and [D-Arg(1),D-Pro(2),D-Trp(7,9),Leu(11)]substance P, a bombesin receptor antagonist. CGRP staining of explants incubated with 24 mM HCO3- maintained no-release levels at and above pH 7.1 but decreased significantly at pH 6.8. The drop was blocked by somatostatin or exclusion of HCO3- and was not augmented by bombesin or 48 mM HCO3-. Results suggest that pulmonary endocrine cells may respond to hypercapnia by releasing bioactive peptides like CGRP, thus stimulating afferent nerves and altering patterns of ventilation and perfusion.
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PMID:Effects of hydrogen and bicarbonate ions on endocrine cells in fetal rat lung organ cultures. 912 67

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

We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). Cerebrovascular reactivity to hypercapnia was not significantly affected. Brain topical superfusion of the muscarinic receptor antagonist atropine (10(-4) M) caused a reduction of CSD hyperperfusion by 41 +/- 13% (n = 5, P < 0.05). The competitive blockade of calcitonin gene-related peptide (CGRP) receptors by CGRP-(8-37) (5 x 10(-7) M) afforded a decrease by 49 +/- 19% (n = 5, P < 0.05), without affecting CO2 reactivity (n = 4). The combined application of both CGRP-(8-37) and atropine further attenuated CSD hyperperfusion (by 69 +/- 17%, n = 5, P < 0.05). After chronic NCN and PSN transection brain topical superfusion of CGRP-(8-37) (5 x 10(-7) M) reduced CSD hyperperfusion slightly by 9.5 +/- 5% (n = 3). Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters.
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PMID:Perivascular nerves contribute to cortical spreading depression-associated hyperemia in rats. 984 81

Cerebrovascular reactivity is severely affected by ischemia, and changes in vascular responses have been reported after cortical spreading depression and head trauma as well. Cortical depolarization (CD) occurs during ischemia, cortical spreading depression, and head trauma, but its effects on cerebrovascular reactivity are unclear. We tested the hypothesis that CD induced by KCl diminishes the vascular responsiveness to various vasodilatory stimuli in piglets. Responses of pial arterioles were determined by changes in vascular diameter by use of a closed cranial window and intravital microscopy. Baseline arteriolar diameters were 105 +/- 3 microm (mean +/- SEM, n = 27). CD was elicited by topical administration of 1 mol/L KCl for 3 min. Vascular responses were measured before and 1 h after CD. KCl elicited CD and constricted arterioles by 54 +/- 4% (n = 27). N-methyl-D-aspartate induced dose-dependent vasodilation that was unaffected by CD; the percent changes were 9 +/- 1 versus 8 +/- 1 (before and after CD) at 10(-5) mol/L, 19 +/- 2 versus 18 +/- 3 at 5 x 10(-5) mol/L, and 29 +/- 2 versus 26 +/- 3 at 10(-4) mol/L (n = 9). Hypercapnic vasodilation was not diminished by CD; the percent changes were 15 +/- 2 versus 16 +/- 4 at 5%, and 27 +/- 5 versus 27 +/- 6 at 10% inspired CO2 (n = 8). Aprikalim and forskolin caused dilation that was also resistant to prior CD; the percent change values were 21 +/- 4 versus 18 +/- 3 and 16 +/- 2 versus 16 +/- 4 at 10(-6) mol/L, 36 +/- 5 versus 34 +/- 5 and 34 +/- 7 versus 37 +/- 7 at 10(-5) mol/L (n = 8), respectively. Finally, calcitonin gene-related peptide-induced vasodilation was unaffected by CD; percent changes were 15 +/- 3 versus 16 +/- 2 at 10(-7) mol/L and 26 +/- 4 versus 22 +/- 3 at 10(-6) mol/L (n = 8). The intact vascular responses after CD suggest that this component is not responsible for decreased cerebrovascular reactivity after ischemia, head trauma, or cortical spreading depression.
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PMID:Cerebrovascular reactivity remains intact after cortical depolarization in newborn piglets. 1036 74

The data, concerning anatomy of brain vessels and the main parameters of cerebral blood flow, including vascular dilation (nitric oxide, prostacyclin, endothelial hyperpolarising factor, estrogen, calcitonin) and vascular contracting (thomboxan A2, endotolin) agents, as well the interaction between them have been scrutinized. Emphasized the leeding role of vascular endothelium and nitric oxide in the regulation of cerebral circulation. Analysis have been done of mechanisms of neuron/vascular conjugent, autoregulation of the brain blood flow, effects of functional loading (hyperoxia, hypoxia, hypercapnia, hypocapnia, acidosis) on the cerebral circulation, the different reactions between them in central and peripheral circulations, oxidant stress, inflammantion. Pointed the significance of these data for the pathogenic mechanisms and therapy of cerebral insult, others physiological and pathophysiologic process in the brain.
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PMID:[Brain blood flow and cerebral insult. Part 2. Regulation of cerebral circulation]. 2380 22

The precise neural circuitry that mediates arousal during sleep apnea is not known. We previously found that glutamatergic neurons in the external lateral parabrachial nucleus (PBel) play a critical role in arousal to elevated CO2 or hypoxia. Because many of the PBel neurons that respond to CO2 express calcitonin gene-related peptide (CGRP), we hypothesized that CGRP may provide a molecular identifier of the CO2 arousal circuit. Here, we report that selective chemogenetic and optogenetic activation of PBelCGRP neurons caused wakefulness, whereas optogenetic inhibition of PBelCGRP neurons prevented arousal to CO2, but not to an acoustic tone or shaking. Optogenetic inhibition of PBelCGRP terminals identified a network of forebrain sites under the control of a PBelCGRP switch that is necessary to arouse animals from hypercapnia. Our findings define a novel cellular target for interventions that may prevent sleep fragmentation and the attendant cardiovascular and cognitive consequences seen in obstructive sleep apnea. VIDEO ABSTRACT.
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PMID:A Genetically Defined Circuit for Arousal from Sleep during Hypercapnia. 2910 5


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