Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. N(G)-monomethyl-L-arginine monoacetate (L-NMMA; 0.1 mM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension that was maintained for 2-2.5 h even following L-NMMA washout. L-NMMA challenge in normal solution (25 mM NaHCO(3); pH 7. 42; pCO(2) 36.9) also induced near maximal tension, although the tension was maintained for only 25 min (mean). Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp (PD145065), homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp (BQ610), and N-cis-2, 6-dimethyl-piperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH(3))-Nle (BQ788; 1-3 microM), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively, completely relaxed the tension that resulted from L-NMMA challenge in hypocapnic or isocapnic alkaline solution. These results demonstrate that constriction due to hypocapnia in vitro can be triggered by an NO synthase inhibitor and is endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction.
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PMID:Hypocapnic constriction in rabbit basilar artery in vitro: triggering by N(G)-monomethyl-L-arginine monoacetate and dependence on endothelin-1 and alkalosis. 1092 29

The role of the L-arginine-nitric oxide (NO) system, the role of the endogenous morphine-like substances (endorphins), and the possible interaction between these two systems in the modulation of regional cerebral and spinal CO2 responsiveness was investigated in anesthetized, ventilated, normotensive, normoxic cats. Regional cerebral blood flow was measured with radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions in nine individual cerebral and spinal cord regions. General opiate receptor blockade by 1 mg/kg naloxone intravenously alone or NO synthase blockade by 3 mg/kg N(omega)-nitro-L-arginine-methyl ester (L-NAME) intravenously alone caused no changes in regional CO2 responsiveness. Combined administration of these two blocking agents in the very same doses, however, resulted in a strong potentiation, with a statistically significant reduction of the CO2 responsiveness observed. Separation of the blood flow response to hypercapnia and hypocapnia indicates that this reduction occurs only during hypercapnia. Specific mu and delta opiate receptors were blocked by 0.5 mg kg(-1) IV beta-funaltrexamine and 0.4 mg kg(-1) IV naltrindole, respectively. The role of specific mu and delta opiate receptors in the NO-opiate interaction was found to be negligible because neither mu nor delta receptor blockade along with simultaneous NO blockade were able to decrease CO2 responsiveness. The current findings suggest a previously unknown interaction between the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) system and the endogenous opiate system in the cerebrovascular bed during hypercapnic stimulation, with the phenomenon not mediated by mu or delta opiate receptors.
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PMID:Interactions between the endothelium-derived relaxing factor/nitric oxide system and the endogenous opiate system in the modulation of cerebral and spinal vascular CO2 responsiveness. 1148 29

Modified Hb solutions have been developed as O(2) carrier transfusion fluids, but of concern is the possibility that increased scavenging of nitric oxide (NO) within the plasma will alter vascular reactivity even if the Hb does not readily extravasate. The effect of decreasing hematocrit from approximately 30% to 18% by an exchange transfusion of a 6% sebacyl cross-linked tetrameric Hb solution on the diameter of pial arterioles possessing tight endothelial junctions was examined through a cranial window in anesthetized cats with and without a NO synthase (NOS) inhibitor. Superfusion of a NOS inhibitor decreased diameter, and subsequent Hb transfusion produced additional constriction that was not different from Hb transfusion alone but was different from the dilation observed by exchange transfusion of an albumin solution after NOS inhibition. In contrast, abluminal application of the cross-linked Hb produced constriction that was attenuated by the NOS inhibitor. Neither abluminal nor intraluminal cross-linked Hb interfered with pial arteriolar dilation to cromakalim, an activator of ATP-sensitive potassium channels. Pial vascular reactivity to hypocapnia and hypercapnia was unaffected by Hb transfusion. Microsphere-determined regional blood flow indicated selective decreases in perfusion after Hb transfusion in the kidney, small intestine, and neurohypophysis, which does not have tight endothelial junctions. Administration of a NOS inhibitor to reduce the basal level of NO available for scavenging before Hb transfusion prevented further decreases in blood flow to these regions compared with NOS inhibition alone. In contrast, blood flow to skeletal and left ventricular muscle increased, and cerebral blood flow was unchanged after Hb transfusion. This cross-linked Hb tetramer is known to appear in renal lymph but not in urine. We conclude that cell-free tetrameric Hb does not scavenge sufficient NO in the plasma space to significantly affect baseline tone in vascular beds with tight endothelial junctions but does produce substantial constriction in beds with porous endothelium. The data support increasing the molecular size of Hb by polymerization or conjugation to limit extravasation in all vascular beds to preserve normal vascular reactivity.
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PMID:Role of nitric oxide scavenging in vascular response to cell-free hemoglobin transfusion. 1589 76