Role of Vasopressin in Altered Pial Artery Responses to Dynorphin and β-Endorphin following Brain Injury

1996 ◽  
Vol 13 (3) ◽  
pp. 115-123 ◽  
Author(s):  
W.M. ARMSTEAD
Keyword(s):  
Brain Injury ◽  
Pial Artery

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.

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.

Role of NOC/oFQ in impaired opioid-induced pial artery dilation following brain injury

2000 ◽  
Vol 869 (1-2) ◽  
pp. 231-235 ◽  
Author(s):  
William M Armstead
Keyword(s):  
Brain Injury ◽  
Pial Artery

scholarly journals NOC/oFQ contributes to age-dependent impairment of NMDA-induced cerebrovasodilation after brain injury

2000 ◽  
Vol 279 (5) ◽  
pp. H2188-H2195 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Brain Injury ◽  
Excitatory Amino Acid ◽  
Age Groups ◽  
Orphanin Fq ◽  
Pial Artery ◽  
Age Related ◽  
Age Dependent

This study characterized the effects of fluid percussion brain injury (FPI) on N-methyl-d-aspartate (NMDA)-induced vasodilation and determined the role of nociceptin/orphanin FQ (NOC/oFQ) in such changes as a function of age and time postinsult. FPI elevated cerebrospinal fluid (CSF) NOC/oFQ from 70 ± 3 to 444 ± 56 pg/ml (≈10−10 M) within 1 h and to 1,931 ± 112 pg/ml within 8 h, whereas values returned to control levels within 168 h in the newborn pig. In contrast, FPI elevated CSF NOC/oFQ from 77 ± 4 to 202 ± 16 pg/ml within 1 h and values returned to control levels within 8 h in the juvenile pig. Topical NOC/oFQ (10−10 M) had no effect on pial artery diameter but attenuated NMDA (10−8, 10−6M)-induced dilation (9 ± 1 and 16 ± 1 vs. 5 ± 1 and 10 ± 1%) in both age groups. In the newborn, NMDA-induced pial artery dilation was reversed to vasoconstriction within 1 h post-FPI and responses remained impaired for 72 h, but such vasoconstriction was attenuated by pretreatment with [F/G]NOC/oFQ(1–13)-NH2 (10−6 M, 1 mg/kg iv), an NOC/oFQ antagonist (9 ± 1 and 16 ± 1 vs. −7 ± 1 and −12 ± 1 vs −2 ± 1 and −3 ± 1% for control, FPI, and FPI pretreated with the NOC/oFQ antagonist). In contrast, in the juvenile, NMDA-induced vasodilation was only attenuated within 1 h post-FPI and returned to control within 8 h. Such dilation was also partially restored by the NOC/oFQ antagonist. These data indicate that NOC/oFQ contributes to impaired NMDA pial artery dilation after FPI. These data suggest that the greater NOC/oFQ release in the newborn versus the juvenile may contribute to age-related differences in FPI effects on excitatory amino acid-induced pial dilation.

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.

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