Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on the increases in cerebral blood flow (CBF) elicited by stepwise elevations in arterial partial pressure of CO2 (PaCO2) from normocapnia up to 204 mmHg. Rats were anesthetized with halothane and ventilated. CBF was monitored over the parietal cortex using a laser-Doppler flowmeter. Increasing levels of hypercapnia elicited graded elevations in CBF that reached a plateau at PaCO2 = 82 +/- 1 mmHg (CBF +215 +/- 25%; n = 8; P < 0.05, analysis of variance). L-NAME (40 mg/kg i.v.; n = 8), but not nitro-D-arginine methyl ester (n = 8), reduced resting CBF (-42 +/- 4%) and attenuated the increase in CBF elicited by hypercapnia. The attenuation occurred only at PaCO2 40-80 mmHg and was maximal (-75 +/- 8%; P < 0.05) at 54 +/- 2 mmHg. At PaCO2 > or = 100 mmHg, L-NAME (40-80 mg/kg) did not attenuate the response (P > 0.05). Reduction of resting CBF (-50 +/- 4%; n = 6) by administration of chloralose (20-40 mg/kg i.v.) did not attenuate the CBF response to hypercapnia (P > 0.05). We also found that the attenuation by L-NAME of resting CBF (n = 5) and of the cerebrovasodilation elicited by hypercapnia (n = 6) has a relatively slow time course, the effects reaching a maximum 45-60 min after intravenous administration of the drug. We conclude that L-NAME does not attenuate the CBF response to CO2 uniformly at all levels of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nitric oxide-dependent and -independent components of cerebrovasodilation elicited by hypercapnia. 751 52

We sought to determine whether the attenuation of the hypercapnic cerebrovasodilation associated with inhibition of nitric oxide synthase (NOS) can be reversed by exogenous NO. Rats were anesthetized (halothane) and ventilated. Neocortical cerebral blood flow (CBF) was monitored by a laser-Doppler probe. The NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg iv) reduced resting CBF [-36 +/- 5% (SE); P < 0.01, analysis of variance] and attenuated the increase in CBF elicited by hypercapnia (partial pressure of CO2 = 50-60 mmHg) by 66% (P < 0.01). L-NAME reduced forebrain NOS catalytic activity by 64 +/- 3% (n = 10; P < 0.001). After L-NAME, intracarotid infusion of the NO donor 3-morpholinosydnonimine (SIN-1; n = 6) increased resting CBF and reestablished the CBF increase elicited by hypercapnia (P > 0.05 from before L-NAME). Similarly, infusion of the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo-cGMP (n = 6) reversed the L-NAME-induced attenuation of the hypercapnic cerebrovasodilation. The NO-independent vasodilator papaverine (n = 6) increased resting CBF but did not reverse the attenuation of the CO2 response. SIN-1 did not affect the attenuation of the CO2 response induced by indomethacin (n = 6). The observation that NO donors reverse the L-NAME-induced attenuation of the CO2 response suggests that a basal level of NO is required for the vasodilation to occur. The findings are consistent with the hypothesis that NO is not the final mediator of smooth muscle relaxation in hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide synthase inhibitors. 751 10

Despite the increasing number of publications devoted to the cerebrovascular role of NO, its precise influence in awake animals is still poorly characterized. The effect of nitric oxide synthase (NOS) inhibition on the cerebrovascular CO2 reactivity was therefore studied in conscious rats. Regional CBF was measured using the [14C]iodoantipyrine technique and brain tissue sampling. The CO2 reactivity was determined 60 min after administration of 30 mg kg-1 N omega-nitro-L-arginine methyl ester (L-NAME). Blockade of NOS by L-NAME significantly decreased CBF in all 11 brain regions studied (-17 to -49%) and increased arterial pressure from 117 +/- 12 to 147 +/- 11 mn Hg. In control conditions, CO2 responsiveness ranged from 1.3 +/- 0.4 in the hypophysis to 6.4 +/- 0.6 ml 100 g-1 min-1 mm Hg-1 in the parietal cortex. Following L-NAME injection, the reactivity to hypercapnia was significantly attenuated in all structures, the magnitude of the reduction ranging from 57% in the medulla to 74% in the cerebellum. This result shows that NO is an important mediator of the hypercapnic vasodilation in the conscious rat.
 ...
PMID:Widespread attenuation of the cerebrovascular reactivity to hypercapnia following inhibition of nitric oxide synthase in the conscious rat. 752 Apr 50

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.
 ...
PMID:Modification of cerebral laser-Doppler flow oscillations by halothane, PCO2, and nitric oxide synthase blockade. 754 53

Inhibition of nitric oxide synthase (NOS) by Nitro-L-arginine-methyl-ester (L-NAME 15 mg and 70 mg/kg i.v.) in 16 male Wistar rats anaesthetized with urethane, paralysed and artificially ventilated, increased significantly local peripheral vascular resistance in the parietal cortex (CVR) along with augmentation of the mean arterial blood pressure (MAP) and no change of the local cerebrocortical blood flow (CBF) recorded with a Laser-Doppler-Flowmeter. In 11 rats L-NAME reversed a pressor effect of brief hypercapnia induced by 10% CO2/air mixture (PaCO2 84.1 +/- 5 mm Hg) into a depressor response, reduced CBF response proportionally to the reduction of MAP and did not influence CVR response to CO2. In 5 rats L-NAME did not abolish the central pressor effect of a CO2-stimulus and significantly augmented CO2-induced vasodilatatory response in the cortex (43.4 +/- 24% before L-NAME and 137.8 +/- 38.8% after L-NAME) by a larger reduction of CVR (-11 +/- 8% before L-NAME and -47.1 +/- 7.6% after L-NAME). It is concluded that NO does not mediate the vasodilatatory effect of brief hypercapnia in the cortex. NO appears critical for the central pressor effect of CO2. In those rats in which the central pressor effect of a CO2-stimulus was not abolished by an NOS blocker, an increased CBF and augmented decrease in CVR was observed during brief hypercapnia. Possible mechanisms of this dual responsiveness of cortical blood flow and arterial blood pressure to CO2, induced by inhibition of NOS, are discussed.
 ...
PMID:Dual response of cerebrocortical blood flow and arterial blood pressure to transient CO2 stimulus after inhibition of nitric oxide synthesis in rats. 754 47

The study was designed to check the role of endogenous NO in maintaining the vasodilatory tone and in mediation of local cerebral blood flow (CBF) responses to CO2 in rostral ventrolateral medulla (RVLM) in the rat. The ventral surface of the medulla was exposed and CBF in the RVLM continuously recorded with a laser-Doppler flowmeter. Local vascular resistance (CVR) was estimated as the ratio of mean arterial pressure (MAP) to CBF. During 1 min exposure to 10% CO2 in oxygen PaCO2 rose from 39.9 +/- 2 mm Hg to 89.7 +/- 4.6 mm Hg and pH fell from 7.4 +/- 0.04 to 7.1 +/- 0.03. After intravenous administration of 15 mg/kg L-NAME (Nitro-L-arginine-methyl ester) MAP increased by 43 +/- 2.9 mm Hg (p < 0.001), local CBF increased by 33 +/- 6% (p < 0.001) and CVR increased by 17 +/- 6% (p < 0.01). L-NAME significantly reduced CBF flow response to 60 s hypercapnia from 47 +/- 9% (p < 0.001) before administration of L-NAME to 14 +/- 5% (p < 0.001). This effect was due to reversal by L-NAME of a pressor response to hypercapnia to a depressor response. The attenuation of CVR response to CO2 by L-NAME was too small to account alone for the significant reduction of local CBF responsiveness to hypercapnia. We conclude that endogenous NO plays a role in maintaining a local vasodilatory tone in RVLM, but it is less significant than in the cortical microcirculation. NO is not a major mediator in the increase in local CBF in RVLM during brief hypercapnia. Endogenous NO is critical for the neurogenic pressor response to brief hypercapnia.
 ...
PMID:Role of the endogenous nitric oxide in the vasodilatory tone and CO2 responsiveness of the rostral ventrolateral medulla microcirculation in the rat. 767 Jan 22

We studied whether the increases in cortical cerebral blood flow (CBF) elicited by stimulation of the cerebellar fastigial nucleus (FN) are attenuated by systemic administration of inhibitors of nitric oxide synthase (NOS) and, if so, whether NOS-containing perivascular nerves arising from the sphenopalatine ganglia (SPG) are the source of NO during FN stimulation. Rats were anesthetized (1-3% halothane) and artificially ventilated. The FN or the pontine reticular formation (PRF) was stimulated electrically through a stereotaxically implanted microelectrode. To eliminate the elevation in arterial pressure (AP) elicited by FN or PRF stimulation the cervical spinal cord was transected and AP was maintained by intravenous phenylephrine. CBF was measured by a laser-Doppler probe placed over the parietal cortex. Systemic administration of the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 5-40 mg/kg) reduced resting CBF, an effect that was maximal at 10 mg/kg (-30 +/- 4%; n = 6; P < 0.003, analysis of variance). L-NAME, but not its inactive isomer D-NAME, attenuated the increases in CBF elicited by FN stimulation or hypercapnia in a dose-dependent fashion (10-40 mg/kg). At 40 mg/kg, the response to FN stimulation was reduced by 80 +/- 6% (n = 6; P < 0.05) and that to hypercapnia was reduced by 70 +/- 9% (P < 0.05). In contrast, the increases in CBF elicited by PRF stimulation were not affected (10-40 mg/kg; P > 0.05; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of nitric oxide synthase-containing vascular nerves in cerebrovasodilation elicited from cerebellum. 768 93

Hypercapnia induces initial constriction and prolonged relaxation of rat small mesenteric arteries. The mechanism of the relaxation is unknown, but has been attributed to lowering of pHi in the vascular smooth muscle. In this study we have investigated the response to raised PCO2 at constant pHo, in mesenteric small arteries precontracted with noradrenaline. 10% CO2 led to a fall in pHi associated with acute potentiation of tension, and subsequent relaxation. The relaxation did not occur in arteries in which the endothelium had been removed, nor in arteries pretreated with the nitric oxide synthase inhibitor, L-NAME (10(-4)M, NG-nitro-L-arginine methyl ester). The D-enantiomer, D-NAME, was without effect. We conclude that hypercapnic-induced vasodilatation in this circulation occurs via endothelium derived nitric oxide production.
 ...
PMID:Carbon dioxide induced vasorelaxation in rat mesenteric small arteries precontracted with noradrenaline is endothelium dependent and mediated by nitric oxide. 768 47

The effect of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (PaCO2 approximately 60 mm Hg and PaCO2 approximately 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety-Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. L-NAME treatment did not have a significant effect on either CMRO2 or CBF under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.
 ...
PMID:Role of nitric oxide in regulating cerebrocortical oxygen consumption and blood flow during hypercapnia. 816 93

The role of nitric oxide (NO) in the cerebral circulation under basal conditions and after vasodilatation to hypercapnia or reactive hyperemias was studied in 17 anesthetized goats. The intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME, 3-4 or 8-10 mg/kg), an inhibitor of nitric oxide production, reduced middle cerebral artery (MCA) flow (electromagnetically measured) by 19 and 30% and increased systemic arterial pressure by 21 and 26%, respectively, whereas heart rate did not significantly change; MCA resistance increased by 48 and 86%, respectively. These hemodynamic effects were reversed by L-arginine (200-300 mg/kg iv; 5 goats). Different levels of hypercapnia (PCO2 of 30-35, 40-45, and 55-65 mmHg) (12 goats) produced arterial PCO2-dependent increases in MCA flow that were similar under control and L-NAME treatment. Graded cerebral hyperemia occurred after 5, 10, and 20 s of MCA occlusion in 5 goats, but its magnitude was decreased during L-NAME treatment. It suggests that, in the cerebral circulation, nitric oxide 1) produces a basal vasodilator tone and 2) is probably not involved in the vasodilatation to hypercapnia but may mediate hyperemic responses after short brain ischemias.
 ...
PMID:Role of NO in goat basal cerebral circulation and after vasodilatation to hypercapnia or brief ischemias. 828 85


1 2 3 4 Next >>