Changes of oxygen tension in brain and somatic tissues induced by vasodilator and vasoconstrictor drugs

Cater, D. B.; Garattini, Silvio; Marina, Filipin; Silver, Ian A.

doi:10.1098/rspb.1961.0061

Cited by 56 publications

(8 citation statements)

References 12 publications

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“…6) demonstrate that reproducing this modest rise in pO 2 in the ex vivo retina does not result in a change in light-evoked vascular responses. Similar small increases in pO 2 have been measured in the brain in vivo during normobaric hyperoxia, where pO 2 rises from ∼12-38 mm Hg to ∼55-90 mm Hg (17)(18)(19)(20)(21). This modest increase in pO 2 likely accounts for why O 2 does not alter neurovascular coupling during hyperoxia in vivo.…”

Section: Discussionsupporting

confidence: 53%

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Oxygen modulation of neurovascular coupling in the retina

Mishra

Hamid

Newman

2011

Proc. Natl. Acad. Sci. U.S.A.

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Neurovascular coupling is a process through which neuronal activity leads to local increases in blood flow in the central nervous system. In brain slices, 100% O 2 has been shown to alter neurovascular coupling, suppressing activity-dependent vasodilation. However, in vivo, hyperoxia reportedly has no effect on blood flow. Resolving these conflicting findings is important, given that hyperoxia is often used in the clinic in the treatment of both adults and neonates, and a reduction in neurovascular coupling could deprive active neurons of adequate nutrients. Here we address this issue by examining neurovascular coupling in both ex vivo and in vivo rat retina preparations. In the ex vivo retina, 100% O 2 reduced light-evoked arteriole vasodilations by 3.9-fold and increased vasoconstrictions by 2.6-fold. In vivo, however, hyperoxia had no effect on light-evoked arteriole dilations or blood velocity. Oxygen electrode measurements showed that 100% O 2 raised pO 2 in the ex vivo retina from 34 to 548 mm Hg, whereas hyperoxia has been reported to increase retinal pO 2 in vivo to only ∼53 mm Hg [Yu DY, Cringle SJ, Alder VA, Su EN (1994) Am J Physiol 267:H2498-H2507]. Replicating the hyperoxic in vivo pO 2 of 53 mm Hg in the ex vivo retina did not alter vasomotor responses, indicating that although O 2 can modulate neurovascular coupling when raised sufficiently high, the hyperoxia-induced rise in retinal pO 2 in vivo is not sufficient to produce a modulatory effect. Our findings demonstrate that hyperoxia does not alter neurovascular coupling in vivo, ensuring that active neurons receive an adequate supply of nutrients.functional hyperemia | glial cells | prostaglandins N euronal activity in the CNS induces local increases in blood flow (1, 2), a homeostatic response termed functional hyperemia. Neurovascular coupling, the process mediating this response, is thought to involve signaling from neurons to glial cells to blood vessels. Neuronal activity induces a rise in intracellular Ca 2+ in glial cell endfeet surrounding vessels, leading to the release of vasoactive arachidonic acid metabolites and resulting in vasomotor responses (2-6). Experiments in brain slices and in the ex vivo retina have revealed that glial activation can evoke both vasodilation and vasoconstriction. Evoked vasodilations are mediated by cyclooxygenase (COX) products (3, 5) and epoxyeicosatrienoic acids (EETs) (6-9), whereas vasoconstrictions are mediated by 20-hydroxyeicosatetraenoic acid (20-HETE) (4,6).A recent study demonstrated that neurovascular coupling is modulated by O 2 in brain slices (10). Both neuronal and glial cell stimulation elicited vasodilations in brain slices exposed to 20% O 2 . In contrast, vasoconstrictions were evoked in the presence of 100% O 2 . However, another recent study reported the opposite effect of O 2 in vivo (11). In that study, increasing systemic O 2 using hyperbaric hyperoxygenation had no effect on cortical functional hyperemia. Resolving these conflicting findings is critical, given that hyperoxia (breat...

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Section: Discussionsupporting

confidence: 53%

“…In contrast, the K m O 2 of both COX1 and COX2 is reportedly ∼10 mm Hg (10 μM) (16), and that of EETs production is <10 mm Hg (14). Therefore, the synthesis of PG and EETs would not be depressed nearly as much as that of 20-HETE at physiological pO 2 levels, which are ∼12-38 mm Hg in the CNS (17)(18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Oxygen modulation of neurovascular coupling in the retina

Mishra

Hamid

Newman

2011

Proc. Natl. Acad. Sci. U.S.A.

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“…In comparison, the oxygen levels found in the hippocampus (100.26 ± 5.76 M) in this study are quite high with hippocampal oxygen being 33.6 mm Hg (∼52.8 M) in the anaesthetised gerbil (Nair et al, 1987) and 20.3 mm Hg (∼31.9 M) in the anaesthetised rat (Cater et al, 1961). Compared to other regions in the rat brain, the hippocampal oxygen levels found here also appear to be higher with 50 M in the caudate nucleus (Zimmerman and Wightman, 1991) and 37 ± 16 M Calia et al, 2009) in the striatum.…”

Section: Discussionmentioning

confidence: 90%

Simultaneous recording of hippocampal oxygen and glucose in real time using constant potential amperometry in the freely-moving rat

Kealy

Bennett

Lowry

2013

Journal of Neuroscience Methods

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h i g h l i g h t sWe show that average concentrations of hippocampal oxygen and glucose are 100.26 ± 5.76 M and 0.60 ± 0.06 mM respectively. We show that there are uncoupled changes in oxygen and glucose during neuronal activation. Anaesthesia and carbonic anhydrase inhibition both significantly increase hippocampal oxygen. Anaesthesia, dimethyl sulfoxide administration and carbonic anhydrase inhibition significantly increase hippocampal glucose. We show that changes in hippocampal metabolism can be detected in real time using constant potential amperometry. a r t i c l e i n f o t r a c tAmperometric sensors for oxygen and glucose allow for real time recording from the brain in freelymoving animals. These sensors have been used to detect activity-and drug-induced changes in metabolism in a number of brain regions but little attention has been given over to the hippocampus despite its importance in cognition and disease. Sensors for oxygen and glucose were co-implanted into the hippocampus and allowed to record for several days. Baseline recordings show that basal concentrations of hippocampal oxygen and glucose are 100.26 ± 5.76 M and 0.60 ± 0.06 mM respectively. Furthermore, stress-induced changes in neural activity have been shown to significantly alter concentrations of both analytes in the hippocampus. Administration of O 2 gas to the animals' snouts results in significant increases in hippocampal oxygen and glucose and administration of N 2 gas results in a significant decrease in hippocampal oxygen. Chloral hydrate-induced anaesthesia causes a significant increase in hippocampal oxygen whereas treatment with the carbonic anhydrase inhibitor acetazolamide significantly increases hippocampal oxygen and glucose. These findings provide real time electrochemical data for the hippocampus which has been previously impossible with traditional methods such as microdialysis or ex vivo analysis. As such, these sensors provide a window into hippocampal function which can be used in conjunction with behavioural and pharmacological interventions to further elucidate the functions and mechanisms of action of the hippocampus in normal and disease states.

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“…For example, also shown in Fig. 4 (#2, open squares) (71)] with gray matter averaging 13 Torr, whereas white matter is lower and cerebral spinal fluid is higher (39,52). During HBO 2 , regional differences in Pti O 2 , similarly, are attributed to differences in neuronal activity, metabolic rate, and cerebral blood flow (71,162,204,(206)(207)(208).…”

Section: Neural Tissue Po 2 In the Intact Mcns During Normoxia And Hymentioning

confidence: 96%

Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures

Dean¹,

Mulkey²,

Garcia³

et al. 2003

Journal of Applied Physiology

175

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III. Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures. J Appl Physiol 95: 883-909, 2003; 10.1152/japplphysiol.00920.2002.-As ambient pressure increases, hydrostatic compression of the central nervous system, combined with increasing levels of inspired PO 2, PCO2, and N2 partial pressure, has deleterious effects on neuronal function, resulting in O 2 toxicity, CO2 toxicity, N2 narcosis, and high-pressure nervous syndrome. The cellular mechanisms responsible for each disorder have been difficult to study by using classic in vitro electrophysiological methods, due to the physical barrier imposed by the sealed pressure chamber and mechanical disturbances during tissue compression. Improved chamber designs and methods have made such experiments feasible in mammalian neurons, especially at ambient pressures Ͻ5 atmospheres absolute (ATA). Here we summarize these methods, the physiologically relevant test pressures, potential research applications, and results of previous research, focusing on the significance of electrophysiological studies at Ͻ5 ATA. Intracellular recordings and tissue PO 2 measurements in slices of rat brain demonstrate how to differentiate the neuronal effects of increased gas pressures from pressure per se. Examples also highlight the use of hyperoxia (Յ3 ATA O 2) as a model for studying the cellular mechanisms of oxidative stress in the mammalian central nervous system. anesthesia; carbon dioxide toxicity; free radicals; high-pressure nervous syndrome; membrane potential; nitrogen narcosis; oxidative stress; oxygen toxicity; polarographic oxygen electrode MOST HUMANS ARE PHYSIOLOGICALLY adapted to live and work near sea level, where ambient pressure is ϳ1 atmosphere absolute (ATA).1 Nonetheless, we exploit a continuum of barometric pressure (PB) ranging from the near vacuum of outer space, which we survive during Space Shuttle extravehicular activity by wearing a 4.3 lb./in.2 absolute (psia) pressure suit (30,300 ft. pressure equivalent, 0.29 ATA) (120, 220), down to the summit of Mt. Everest at 29,029 ft., where PB is 0.31 ATA (221), to ocean depths as great as 2,300 ft. of sea water (fsw), where PB increases to ϳ70 ATA (18). These situations are the pressure extremes of our inhabitable environment, which only relatively few highly trained individuals have ever occupied.Military personnel, medical personnel, and other humans, however, frequently encounter levels of hyperbaric pressure (i.e., Ͼ1 ATA) of lesser degrees in their normal work environments. Examples of moderate hyperbaric environments (e.g., Ͻ5 ATA) include the following: patients and medical attendants undergoing hyperbaric O 2 therapy (HBOT) (38,203); diving with an underwater breathing apparatus for recreational, professional (oil and salvage companies), and combat purposes (89); simulated dry and wet dives for hyperbaric research and dive training (217); and working in the compressed atmosphere of a subterranean environment (117). Abnormal work environments resulting from catastrophic accident...

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Changes of oxygen tension in brain and somatic tissues induced by vasodilator and vasoconstrictor drugs

Cited by 56 publications

References 12 publications

Oxygen modulation of neurovascular coupling in the retina

Oxygen modulation of neurovascular coupling in the retina

Simultaneous recording of hippocampal oxygen and glucose in real time using constant potential amperometry in the freely-moving rat

Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures

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