Role of endothelin in pial artery vasoconstriction and altered responses to vasopressin after brain injury

1996 ◽  
Vol 85 (5) ◽  
pp. 901-907 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Brain Injury ◽  
Content Type ◽  
Endothelin 1 ◽  
Cranial Window ◽  
Pial Artery ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
Before And After ◽  
Newborn Pigs

✓ Pial artery constriction following fluid-percussion injury to the brain is associated with elevated cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs. It has also been observed that fluid-percussion injury reverses the function of vasopressin from that of a dilator to a constrictor. Endothelin-1 (ET-1), a purported mediator of cerebral vasospasm, can be released by several stimuli, including vasopressin. The present study was designed to investigate the role of ET-1 in pial artery constriction and in the reversal of vasopressin from a dilator to a constrictor, which is observed after fluid-percussion injury. Brain injury of moderate severity (1.9–2.3 atm) was produced in anesthetized newborn pigs that had been equipped with a closed cranial window. Endothelin-1 elicited pial dilation at low concentrations and vasoconstriction at higher concentrations. Fluid-percussion injury reversed the process of dilation to that of constriction at the low ET-1 concentration and potentiated this constriction at high ET-1 concentrations (10% ± 1%, −8% ± 1%, and −15% ± 1% vs. −6% ± 1%, −17% ± 1%, and −26% ± 2% for 10−12, 10−10, 10−8 M ET-1 before and after fluid-percussion injury, respectively). Vasopressin modestly increased CSF ET-1 concentration before fluid-percussion injury. Fluid-percussion injury markedly increased CSF ET-1 concentration and the ability of vasopressin to release ET-1 (20 ± 2, 26 ± 3, and 40 ± 4 pg/ml vs. 93 ± 6, 141 ± 9, and 247 ± 31 pg/ml for control, 40 pg/ml vasopressin, and 400 pg/ml vasopressin before and after fluid-percussion injury, respectively). An ET-1 antagonist, BQ 123 (10−6 M) blunted pial artery constriction following fluid-percussion injury (146 ± 5 µm−127 ± 6 µm vs. 144 ± 5 µm−136 ± 4 µm). The BQ 123 also blocked the reversal of vasopressin's function from that of a dilator to a constrictor after fluid-percussion injury (8% ± 1%, 21% ± 3%, and −5% ± 1%, −14% ± 2% vs. 8% ± 1%, 21% ± 2% and 4% ± 1%, 2% ± 1% for 40 and 4000 pg/ml vasopressin before and after fluid-percussion injury in the absence and presence of BQ 123, respectively). The BQ 123 blocked the constrictor component to ET-1, whereas it had no effect on the dilator component. These data show that ET-1 contributes to pial constriction after fluid-percussion injury. These data also indicate that vasopressin-induced release of ET-1 contributes to the reversal of vasopressin from a dilator to a constrictor following fluid-percussion injury. Furthermore, these data indicate that elevated CSF vasopressin and ET-1 interact in a positive feedback manner to promote pial artery constriction following fluid-percussion injury.

Influence of brain injury on vasopressin-induced pial artery vasodilation: role of superoxide anion

1996 ◽  
Vol 270 (4) ◽  
pp. H1272-H1278 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Brain Injury ◽  
Superoxide Anion ◽  
Biochemical Changes ◽  
Superoxide Anion Generation ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Radical Generation ◽  
Cylindrical Reservoir

The present study was designed to investigate the effect of fluid percussion brain injury (FPI) on vasopressin-induced pial artery vasodilation and the role of superoxide anion generation in those observed effects. In the piglet, it was observed previously the FPI produces pial artery constriction associated with free radical generation. Anesthetized piglets equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. FPI of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Vasopressin in physiological and pharmacological concentrations (10 and 1,000 microU/ml) produced vasodilation that was reversed to constriction after FPI (15 +/- 1 vs. -8 +/- 1 and 25 +/- 1 vs. 13 +/- 1% for 10 and 1,000 microU/ml before and after injury, respectively). Vasopressin-induced dilation was associated with increased cerebrospinal fluid guanosine 3', 5'-cyclic monophosphate, and these biochemical changes were blunted by FPI (407 +/- 12 and 720 +/- 28 vs. 4 and 272 +/- 5 fmol/ml for control and 10 microU/ml before and after injury, respectively). In contrast, polyethylene glycol superoxide dismutase (PEG-SOD) and catalase pretreatment 30 min before FPI partially restored vasopressin-induced pial artery dilation (14 +/- 1 vs. 3 +/- 1 and 22 +/- 1 vs. 2 +/- 4% for 10 and 1,000 microU/ml before and after FPI, respectively). Similarly, biochemical changes associated with vasopressin dilation were also partially restored by PEG-SOD and catalase after FPI. These data show that vasopressin is reversed from a dilator to a vasoconstrictor after FPI and suggests the superoxide anion generation contributes to the alteration of vasopressin cerebrovascular effects after injury and that such altered vasopressin cerebrovascular effects contribute to pial vasoconstriction after FPI.

ATP-dependent K+ channel activation reduces loss of opioid dilation after brain injury

1998 ◽  
Vol 274 (5) ◽  
pp. H1674-H1683 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Brain Injury ◽  
K Channel ◽  
Channel Activation ◽  
Calcium Dependent ◽  
Cranial Window ◽  
Pial Artery ◽  
Cgmp Analog ◽  
Newborn Pigs ◽  
The Brain

ATP-dependent K+(KATP) channel function is impaired after fluid percussion brain injury (FPI). Additionally, the nitric oxide (NO) releaser sodium nitroprusside and a cGMP analog elicit pial dilation via KATP channel activation, whereas opioids such as methionine enkephalin (Met) elicit pial dilation via NO and KATP channel activation. Decremented Met dilation contributes to reductions in pial artery diameter and altered cerebral hemodynamics after FPI. This study was designed to investigate the role of KATP channel activation before FPI in the loss of opioid dilation subsequent to FPI in newborn pigs equipped with a closed cranial window. FPI was produced by allowing a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw in the cranium. FPI blunted dilation to Met (7 ± 1, 11 ± 1, and 17 ± 1% before FPI vs. 1 ± 1, 4 ± 1, and 6 ± 1% after FPI for 10−10, 10−8, and 10−6 M Met, respectively). Met-associated elevation in cerebrospinal fluid (CSF) cGMP was similarly blunted (350 ± 12 and 636 ± 12 fmol/ml before FPI vs. 265 ± 5 and 312 ± 17 fmol/ml after FPI for control and 10−6 M Met, respectively). In piglets pretreated with cromakalim (10−10 M) 20 min before FPI, Met dilation was partially restored (7 ± 1, 10 ± 1, and 15 ± 1% before FPI vs. 4 ± 1, 7 ± 1, and 11 ± 1% after FPI for 10−10, 10−8, and 10−6 M Met, respectively). Met cGMP release was similarly partially restored (400 ± 9 and 665 ± 25 fmol/ml before FPI vs. 327 ± 11 and 564 ± 23 fmol/ml after FPI for control and 10−6 Met, respectively). Cromakalim (10−10 M) had no effect on pial diameter itself but prevented pial artery constriction by FPI (148 ± 5 to 124 ± 5 μm vs. 139 ± 4 to 141 ± 4 μm in the absence vs. presence of cromakalim pretreatment, respectively). In contrast, pretreatment with a subthreshold concentration of NS-1619, a calcium-dependent K+ channel agonist, did not restore vascular and biochemical parameters after FPI. These data indicate that prior KATP channel activation reduces the loss of opioid dilation after FPI.

Influence of brain injury on opioid-induced pial artery vasodilation

1995 ◽  
Vol 269 (5) ◽  
pp. H1776-H1783
Author(s):  
M. C. Thorogood ◽  
W. M. Armstead
Keyword(s):  
Brain Injury ◽  
No Synthase ◽  
Opioid Agonist ◽  
Mu Opioid ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Newborn Pigs ◽  
Synthase Inhibitor ◽  
Cylindrical Reservoir

This study was designed to investigate the effect of fluid percussion brain injury on opioid-induced pial artery vasodilation in the newborn pig. Previous observations have shown that brain injury produces pial artery vasoconstriction associated with elevated cerebral spinal fluid (CSF) opioid levels in the piglet. Additionally, opioids produce pial vasodilation that is attenuated by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). Anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Methionine enkephalin (Met), an endogenous mu-opioid agonist in physiological and pharmacological concentrations (10(-10), 10(-8), 10(-6) M), produced vasodilation that was attenuated following brain injury (7 +/- 1 vs. 3 +/- 1%, 11 +/- 1 vs. 5 +/- 1% and 16 +/- 1 vs. 8 +/- 1% for 10(-10), 10(-8), 10(-6) M Met before and after injury, respectively, n = 5). Met-induced dilation was associated with increased cortical periarachnoid CSF guanosine 3',5'-cyclic monophosphate (cGMP), and these biochemical changes were blunted by brain injury (342 +/- 12 and 640 +/- 13 fmol/ml vs. 267 +/- 6 and 321 +/- 17 fmol/ml for control and Met 10(-6) M before and after injury, respectively, n = 5). Leucine enkephalin, an endogenous delta-agonist, induced pial dilation and associated changes in CSF cGMP, which were similarly altered by brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Adrenomedullin Reduces Gender-Dependent Loss of Hypotensive Cerebrovasodilation after Newborn Brain Injury through Activation of ATP-Dependent K Channels

2007 ◽  
Vol 27 (10) ◽  
pp. 1702-1709 ◽  
Author(s):  
William M Armstead ◽  
Monica S Vavilala
Keyword(s):  
Brain Injury ◽  
Clinical Intervention ◽  
K Channel ◽  
Dependent Manner ◽  
Channel Activation ◽  
Cranial Window ◽  
Pial Artery ◽  
Newborn Brain ◽  
Newborn Pigs

Cerebrovascular dysregulation during hypotension occurs after fluid percussion brain injury (FPI) in the newborn pig owing to impaired K channel function. This study was designed to (1) determine the role of gender and K channel activation in adrenomedullin (ADM) cerebrovasodilation, (2) characterize the role of gender in the loss of hypotensive cerebrovasodilation after FPI, and (3) determine the role of gender in the ability of exogenous ADM to modulate hypotensive dysregulation after FPI. Lateral FPI (2 atm) was induced in newborn male and female newborn pigs (1 to 5 days old) equipped with a closed cranial window, n = 6 for each protocol. Adrenomedullin-induced pial artery dilation was significantly greater in female than male piglets and blocked by the KATP channel antagonist glibenclamide, but not by the Kca channel antagonist iberiotoxin. Cerebrospinal fluid ADM was increased from 3.8 ± 0.7 to 14.6 ± 3.0 fmol/mL after FPI in female but was unchanged in male piglets. Hypotensive pial artery dilation was blunted to a significantly greater degree in male versus female piglets after FPI. Topical pretreatment with a subthreshold vascular concentration of ADM (10−10 mol/L) before FPI reduced the loss of hypotensive pial artery dilation in both genders, but protection was significantly greater in male versus female piglets. These data show that hypotensive pial artery dilation is impaired after FPI in a gender-dependent manner. By unmasking a gender-dependent endogenous protectant, these data suggest novel gender-dependent approaches for clinical intervention in the treatment of perinatal traumatic brain injury.

Heat shock protein modulation of KATPand KCachannel cerebrovasodilation after brain injury

2005 ◽  
Vol 289 (3) ◽  
pp. H1184-H1190 ◽  
Author(s):  
William M. Armstead ◽  
James G. Hecker
Keyword(s):  
Brain Injury ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Hsp 70 ◽  
Cranial Window ◽  
Pial Artery ◽  
Hsp 27 ◽  
Newborn Pigs ◽  
Csf Concentration

Fluid percussion brain injury (FPI) impairs pial artery dilation to activators of the ATP-sensitive (KATP) and calcium-activated (KCa) K+channels. This study investigated the role of heat shock protein (HSP) in the modulation of K+channel-induced pial artery dilation after FPI in newborn pigs equipped with a closed cranial window. Under nonbrain injury conditions, topical coadministration of exogenous HSP-27 (1 μg/ml) blunted dilation to cromakalim, CGRP, and NS-1619 (10−8and 10−6M; cromakalim and CGRP are KATPagonists and NS-1619 is a KCaagonist). In contrast, coadministration of exogenous HSP-70 (1 μg/ml) potentiated dilation to cromakalim, CGRP, and NS-1619. FPI increased the cerebrospinal fluid (CSF) concentration of HSP-27 from 0.051 ± 0.012 to 0.113 ± 0.035 ng/ml but decreased the CSF concentration of HSP-70 from 50.42 ± 8.96 to 30.9 ± 9.9 ng/ml at 1 h postinsult. Pretreatment with topical exogenous HSP-70 (1 μg/ml) before FPI fully blocked injury-induced impairment of cromakalim and CGRP dilation and partially blocked injury-induced impairment of dilation to NS-1619. These data indicate that HSP-27 and HSP-70 contribute to modulation of K+channel-induced pial artery dilation. These data suggest that HSP-70 is an endogenous protectant of which its actions may be unmasked and/or potentiated with exogenous administration before brain injury.

scholarly journals Role of opioids in hypoxic pial artery dilation is stimulus duration dependent

1998 ◽  
Vol 275 (3) ◽  
pp. H861-H867 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Stimulus Duration ◽  
Exposure Period ◽  
Hypoxic Exposure ◽  
Relative Role ◽  
Moderate Hypoxia ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After

Because methionine enkephalin contributes to and dynorphin opposes dilation during a 10-min hypoxic exposure, opioids modulate pial artery dilation to this stimulus. However, such modulation may be dependent on the duration of hypoxia. The present study was designed to characterize the modulation of hypoxic pial dilation by opioids as a function of stimulus duration in newborn pigs equipped with a closed cranial window. Hypoxic dilation was decremented in both moderate and severe groups ([Formula: see text] ≈ 35 and 25 mmHg, respectively) during 20-min and 40-min exposure periods compared with the response during 5 or 10 min of stimulation (24 ± 1, 25 ± 1, 18 ± 1, and 14 ± 1% for 5, 10, 20, and 40 min of moderate hypoxia; means ± SE). Moderate and severe hypoxia had no effect on cerebral spinal fluid (CSF) methionine enkephalin or dynorphin concentration during a 5-min exposure period. During a 10-min exposure, however, both opioids were increased in CSF. During 20- and 40-min exposure periods, CSF dynorphin continued to increase, whereas methionine enkephalin steadily decreased (962 ± 18, 952 ± 21, 2,821 ± 15, 2,000 ± 81, and 1,726 ± 58 pg/ml methionine enkephalin for control, 5, 10, 20, and 40 min of moderate hypoxia, respectively). The μ-opioid (methionine enkephalin) antagonist β-funaltrexamine had no influence on dilation during the 5-min exposure, decremented the 10- and 20-min exposures, but had no effect on 40-min exposure hypoxic dilation. Whereas the κ-opioid (dynorphin) antagonist norbinaltorphimine similarly had no effect on a 5-min exposure dilation, it, in contrast, potentiated 10-, 20-, and 40-min exposure hypoxic dilations (23 ± 1 vs. 23 ± 1, 24 ± 1 vs. 32 ± 1, 16 ± 1 vs. 24 ± 2, and 13 ± 1 vs. 23 ± 3% for 5, 10, 20, and 40-min hypoxic dilation before and after norbinaltorphimine). These data show that opioids do not modulate hypoxic pial dilation during short but do so during longer exposure periods. Moreover, hypoxic pial dilation is diminished during longer exposure periods. Decremented hypoxic pial dilation during longer exposure periods results, at least in part, from decreased release of methionine enkephalin and accentuated release of dynorphin. These data suggest that the relative role of opioids in hypoxic pial dilation changes with the stimulus duration.

Relationship among NO, the KATP channel, and opioids in hypoxic pial artery dilation

1998 ◽  
Vol 275 (3) ◽  
pp. H988-H994 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Katp Channel ◽  
No Synthase ◽  
Channel Activation ◽  
Cranial Window ◽  
Pial Artery ◽  
Sequential Release ◽  
No Release ◽  
Before And After ◽  
Newborn Pigs ◽  
Synthase Inhibitor

Nitric oxide (NO), opioids, and ATP-sensitive K+(KATP) channel activation contribute to hypoxia-induced pial artery dilation. NO releasers and cGMP analogs increase opioid concentration in cerebrospinal fluid (CSF) and elicit dilation via KATPchannel activation. Opioids themselves also elicit dilation via KATP channel activation. This study was designed to investigate the relationships among the above mechanisms in hypoxic pial artery dilation using newborn pigs equipped with a closed cranial window. Cromakalim (10−8 and 10−6 M), a KATP agonist, produced dilation that was unchanged by the NO synthase inhibitor N-nitro-l-arginine (l-NNA, 10−6 and 10−3 M): 13 ± 1 and 31 ± 1 vs. 14 ± 1 and 31 ± 1% before and after 10−3 Ml-NNA. Cromakalim dilation also was not associated with increased CSF cGMP and was unchanged by the Rp diastereomer of 8-bromoguanosine 3′,5′-cyclic monophosphothioate, a cGMP antagonist. Glibenclamide (10−6 M), a KATP antagonist, attenuated hypoxic dilation but hypoxia-associated CSF cGMP release was unchanged: 457 ± 12 and 935 ± 30 vs. 458 ± 11 and 921 ± 22 fmol/ml. Coadministration ofl-NNA with glibenclamide had no further effect on the already diminished hypoxic dilation but blocked the hypoxia-associated rise in CSF cGMP. Cromakalim had no effect on CSF methionine enkephalin: 1,012 ± 28 and 1,062 ± 32 pg/ml. These data show that KATP channel agonists do not elicit dilation via NO/cGMP and do not release opioids. NO release during hypoxia also is independent of KATP channel activation. These data suggest that hypoxic dilation results from the sequential release of NO, cGMP, and opioids, which in turn activate the KATP channel.

Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain

1980 ◽  
Vol 53 (4) ◽  
pp. 500-511 ◽  
Author(s):  
W. Lewelt ◽  
L. W. Jenkins ◽  
J. Douglas Miller
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Severe Injury ◽  
Content Type ◽  
Fluid Percussion ◽  
Arterial Blood ◽  
Fluid Percussion Injury ◽  
The Brain

✓ To test the hypothesis that concussive brain injury impairs autoregulation of cerebral blood flow (CBF), 24 cats were subjected to hemorrhagic hypotension in 10-mm Hg increments while measurements were made of arterial and intracranial pressure, CBF, and arterial blood gases. Eight cats served as controls, while eight were subjected to mild fluid percussion injury of the brain (1.5 to 2.2 atmospheres) and eight to severe injury (2.8 to 4.8 atmospheres). Injury produced only transient changes in arterial and intracranial pressure, and no change in resting CBF. Impairment of autoregulation was found in injured animals, more pronounced in the severe-injury group. This could not be explained on the basis of intracranial hypertension, hypoxemia, hypercarbia, or brain damage localized to the area of the blood flow electrodes. It is, therefore, concluded that concussive brain injury produces a generalized loss of autoregulation for at least several hours following injury.

Opioids contribute to hypoxia-induced pial artery dilation through activation of ATP-sensitive K+ channels

1995 ◽  
Vol 269 (3) ◽  
pp. H997-H1002 ◽  
Author(s):  
V. Shankar ◽  
W. M. Armstead
Keyword(s):  
Severe Hypoxia ◽  
Methionine Enkephalin ◽  
K Channels ◽  
Leucine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Window Technique ◽  
Before And After ◽  
Newborn Pigs ◽  
Arterial Po2

It has been previously observed that hypoxia increases cerebrospinal fluid (CSF) methionine enkephalin and leucine enkephalin levels, and these opioids contribute to hypoxia-induced pial artery vasodilation. The present study was designed to investigate whether the activation of ATP-sensitive K+ channels (KATP) mediates the contribution of opioids to the hypoxia-induced pial artery dilation. The closed-cranial window technique was used to measure pial diameter in newborn pigs. Glibenclamide (10(-6) M), a KATP inhibitor, attenuated the dilation resulting from moderate and severe hypoxia [23 +/- 1 and 33 +/- 2% vs. 7 +/- 1 and 18 +/- 2%, respectively, for moderate and severe hypoxia (arterial PO2 approximately 35 and 25 mmHg, respectively) in the absence vs. presence of glibenclamide]. In addition, glibenclamide attenuated the dilation produced by methionine enkephalin (10(-8) and 10(-6) M) (13 +/- 1 vs. 4 +/- 2% and 21 +/- 2 vs. 7 +/- 3%, respectively, for methionine enkephalin in the absence and presence of glibenclamide). Leucine enkephalin-induced dilation was similarly attenuated by glibenclamide. Cromakalim (10(-8) and 10(-6) M), a KATP agonist, produced dilation that was blocked by glibenclamide (12 +/- 1 and 25 +/- 1 vs. 3 +/- 1 and 5 +/- 1% before and after glibenclamide, respectively). These data show that activation of KATP contributes to methionine enkephalin- and leucine enkephalin-induced dilation. Furthermore, these observations suggest that opioids contribute to hypoxia-induced pial artery dilation via KATP activation.

Permissive role of prostacyclin in cerebral vasodilation to hypercapnia in newborn pigs

1994 ◽  
Vol 267 (1) ◽  
pp. H285-H291 ◽  
Author(s):  
C. W. Leffler ◽  
R. Mirro ◽  
L. J. Pharris ◽  
M. Shibata
Keyword(s):  
Sodium Nitroprusside ◽  
Co2 Partial Pressure ◽  
Cranial Window ◽  
Prostacyclin Receptor ◽  
Artificial Cerebrospinal Fluid ◽  
Before And After ◽  
Newborn Pigs ◽  
Cerebral Vasodilation ◽  
Prostanoid Synthesis

Hypercapnic cerebral vasodilation in piglets is accompanied by increased cerebral prostanoid synthesis. Interventions that prevent the increased prostanoids also interfere with the vasodilation. However, the increased prostanoids may not produce vasodilation directly; instead, they may allow or enhance function of another mechanism. The present experiments examined the hypothesis that prostacyclin can allow, but may not directly produce, cerebral vasodilation to hypercapnia. Chloralose-anesthetized piglets were equipped with closed cranial windows for measurements of pial arteriolar diameters. Hypercapnia (arterial CO2 partial pressure approximately 70 mmHg) was administered before and after indomethacin (5 mg/kg iv) in all animals. Then artificial cerebrospinal fluid (aCSF) under the cranial window was replaced for the remainder of the experiment with aCSF containing vehicle, carbaprostacyclin (60 pM), iloprost (1 pM), prostaglandin E2 (PGE2; 1.7 and 3.3 nM), isoproterenol (10 and 100 nM), or sodium nitroprusside (1 microM), and hypercapnia was repeated. The two prostacyclin receptor agonists restored cerebral vasodilation to hypercapnia that had been blocked by indomethacin (to 92 +/- 31% and 76 +/- 11% of the before-indomethacin dilation for carbaprostacyclin and iloprost, respectively.) The highest dose of PGE2 partially restored the dilation (43 +/- 7% of the pre-indomethacin response). In contrast, neither isoproterenol nor sodium nitroprusside permitted significant dilation to hypercapnia following indomethacin treatment. These data indicate that prostacyclin can allow hypercapnic vasodilation to occur, but increasing levels do not appear to be necessary to cause the dilation directly. The short half-life of prostacyclin may explain why active prostanoid synthesis appears to be necessary for hypercapnia-induced cerebral vasodilation in newborn pigs.

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