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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

In this study, we tested the hypothesis that nitric oxide (NO) and adenosine (ADO) are the principal mediators of severe hypoxia-induced vasodilation. In addition, we examined whether activation of N-methyl-D-aspartate (NMDA) receptors and/or perivascular nerves plays a role. A closed cranial window and intravital microscopy system was used to monitor diameter changes in pial arterioles (approximately 40 microns) in anesthetized rats. The relative contributions of ADO, NMDA, NO, and neuronal activation to hypoxic cerebrovasodilation were assessed using the blockers 8-sulfophenyltheophylline (8-SPT), MK-801, nitro-L-arginine methylester (L-NAME), and tetrodotoxin (TTX). Two experimental series were studied. In the first, we tested the effects of NOS inhibition, via topical L-NAME (1 mM), on moderate (PaO2 approximately 46 mmHg) then severe (PaO2 approximately 34 mmHg) hypoxia-induced dilation. To confirm that L-NAME was affecting specifically NO-dependent responses, we also examined, in each experiment, the vasodilatory responses to topical applications of NOS-dependent (adenosine diphosphate (ADP); acetylcholine (ACh)) and -independent (sodium nitroprusside (SNP)) agents, in the presence of L-NAME or, in controls, the presence of D-NAME or no added analogue. In the second series, topical suffusions of ADP, ADO, and NMDA were sequentially applied, followed by 5 min exposure to severe hypoxia (PaO2 approximately 32 mmHg). Following return to normoxia, a suffusion of either 8-SPT (10 microM), MK-801 (10 microM), TTX (1 microM), or 8-SPT+MK-801 was initiated (or, in controls, application of a drug-free suffusate was maintained), and the above sequence repeated. In control, TTX, and 8-SPT+MK-801 experiments, baseline conditions were then restored and hypercapnia (PaCO2 = 70-85 mmHg) was imposed. In the series 1 control groups, moderate and severe hypoxia elicited approximately 20% and 35-40% increases in diameter, respectively. L-NAME attenuated ADP- and ACh-induced dilations, did not alter the arteriolar responses to SNP or moderate hypoxia, but prevented further dilation upon imposition of severe hypoxia. This suggested that 45-50% of the severe hypoxia response was NO-dependent. In series 2, 8-SPT blocked the adenosine response and reduced severe hypoxia-induced dilation by 46%. MK-801 predictably blocked NMDA-induced relaxation and reduced the hypoxic response by 42%. When combined, 8-SPT and MK-801 affected hypoxic vasodilation additively. After TTX, the ADP and ADO responses were normal, but NMDA and hypoxia responses were completely blocked. Hypercapnia-induced dilation was unaffected by TTX or 8-SPT+MK-801. The results imply that severe hypoxia-induced release of NO and ADO, and the accompanying pial arteriolar dilation, are wholly dependent on the capacity to generate action potentials in perivascular nerves. The similarity of the L-NAME and MK-801 effects on hypoxic cerebrovasodilation suggests that the NO-dependency, to a large degree, derives from NMDA receptor activation.
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PMID:Role of nitric oxide, adenosine, N-methyl-D-aspartate receptors, and neuronal activation in hypoxia-induced pial arteriolar dilation in rats. 875 Sep 62