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.

Vasopressin contributes to dynorphin modulation of hypoxic cerebrovasodilation

1998 ◽  
Vol 275 (6) ◽  
pp. H2072-H2079 ◽  
Author(s):  
Andrew Venteicher ◽  
William M. Armstead
Keyword(s):  
Cerebrospinal Fluid ◽  
Stimulus Duration ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Vascular Response ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Newborn Pigs

Because pial artery dilation during a 20- or 40-min hypoxic exposure was less than that observed during a 5- or 10-min exposure, stimulus duration determines the vascular response to hypoxia. Dynorphin (Dyn) modulates hypoxic pial dilation and contributes to decremented dilation during longer hypoxic exposures. This study was designed to determine whether vasopressin (VP) contributes to Dyn modulation of hypoxic pial dilation in newborn pigs equipped with a closed cranial window. Moderate (M) and severe (S) hypoxia (arterial [Formula: see text] ∼ 35 and 25 mmHg, respectively) had no effect on cerebrospinal fluid VP during a 5-min exposure but increased its concentration during longer exposure periods. The VP antagonist [β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2,Arg8]vasopressin (MEAVP) had no influence on pial dilation during the 5-min exposure but potentiated the 20- and 40-min M and S hypoxic exposure dilations: 21 ± 2 vs. 29 ± 3% and 23 ± 2 vs. 33 ± 2% for 20- and 40-min S hypoxic dilation before and after MEAVP. Topical VP during 5 min of hypoxia elicited dilation that was reversed to vasoconstriction during 20 min of S and 40 min of M and S hypoxia. Similarly, during 5 min of hypoxia, Dyn elicited dilation that was reversed to vasoconstriction during longer hypoxic periods. MEAVP blunted this Dyn-induced vasoconstriction. These data show that VP modulates hypoxic pial dilation in a stimulus duration-dependent manner and that VP contributes to the reversal of Dyn from a dilator to a constrictor during prolonged hypoxia. Finally, these data suggest that VP contributes to Dyn modulation of hypoxic cerebrovasodilation.

scholarly journals Role of Endothelial Nitric Oxide Synthase in Hypoxia-Induced Pial Artery Dilation

1998 ◽  
Vol 18 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Michael J. Wilderman ◽  
William M. Armstead
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Endothelial No Synthase ◽  
Before And After ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent release of methionine enkephalin and leucine enkephalin in the newborn pig. In separate studies, these opioids also were observed to elicit NO-dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to investigate the role of the endothelial isoform of NO synthase in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. N-iminoethyl-l-ornithine (l-NIO) (10−6 mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited by hypoxia (Po2 ≈ 35 mm Hg) (24 ± 2 versus 24 ± 2% in the absence and presence of l-NIO, respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP, which also was unchanged in the presence of l-NIO (394 ± 19 and 776 ± 63 versus 323 ± 13 and 739 ± 25 fmol/mL for control and hypoxia in the absence and presence of l-NIO, respectively, n = 6). Additionally, hypoxic pial dilation was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of l-NIO (992 ± 73 and 2469 ± 197 versus 984 ± 18 and 2275 ± 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin–induced dilation was blocked by l-NIO (6 ± 1, 10 ± 1, and 16 ± 1 versus 1 ± 1, 1 ± 1, and 2 ± 1% for 10−10, 10−8, 10−6 mol/L methionine enkephalin, respectively, before and after l-NIO, n = 8). Substance P–induced pial dilation was blunted by l-NIO, whereas responses to sodium nitroprusside and N-methyl-d-aspartate were unchanged. These data indicate that endothelial NO synthase contributes to opioid-induced pial artery dilation but not hypoxia-induced dilation. Additionally, these data suggest that neuronally derived NO contributes to hypoxic pial dilation.

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.

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.

Role of nitric oxide and cAMP in prostaglandin-induced pial arterial vasodilation

1995 ◽  
Vol 268 (4) ◽  
pp. H1436-H1440 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Topical Administration ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Arterial Dilation ◽  
Synthase Inhibitor

The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to prostaglandin (PG)I2 and PGE2 in newborn pigs equipped with a closed cranial window. PGI2 (1–100 ng/ml) produced pial arterial dilation that was blunted by nitro-L-arginine (L-NNA, 10(-6) M), an NO synthase inhibitor (9 +/- 1 vs. 2 +/- 1%, 21 +/- 1 vs. 5 +/- 3% for 1 and 100 ng/ml PGI2 respectively, n = 6; means +/- SE). PGI2-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in cGMP were blocked by L-NNA (386 +/- 8 and 1,054 +/- 30 fmol/ml vs. 266 +/- 6 and 274 +/- 4 fmol/ml for control and PGI2 100 ng/ml before and after L-NNA respectively, n = 6). In contrast, PGI2-associated changes in CSF cAMP were unchanged by L-NNA (1,021 +/- 25 and 2,703 +/- 129 fmol/ml vs. 980 +/- 23 and 2,636 +/- 193 fmol/ml for control, PGI2 100 ng/ml before and after L-NNA, respectively, n = 6). PGE2 elicited similar changes in pial artery diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also being similarly inhibited by L-NNA. After L-NNA, topical administration of the NO donor sodium nitroprusside (SNP, 10(-9) M) increased pial artery diameter up to the resting level before L-NNA and partially restored the vasodilation elicited by PGI2 and PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

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 nitric oxide and cAMP in beta-adrenoceptor-induced pial artery vasodilation

1995 ◽  
Vol 268 (3) ◽  
pp. H1071-H1076 ◽  
Author(s):  
S. Rebich ◽  
J. O. Devine ◽  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Beta Agonist ◽  
Cyclic Monophosphate ◽  
Beta Adrenoceptor ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Adrenoceptor Agonists ◽  
Synthase Inhibitor

The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to beta-adrenoceptor agonists in newborn pigs equipped with a closed cranial window. Dobutamine (10(-8) and 10(-6) M), a beta 1-agonist, produced pial artery dilation that was blunted by NG-nitro-L-arginine (L-NNA; 10(-6) M), a NO synthase inhibitor (12 +/- 1 vs. 0 +/- 2% and 24 +/- 3 vs. 4 +/- 1% for 10(-8) and 10(-6) M dobutamine, respectively). Dobutamine-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in CSF cGMP were blocked by L-NNA (391 +/- 10 and 675 +/- 36 fmol/ml vs. 307 +/- 3 and 346 +/- 37 fmol/ml for control and 10(-6) M dobutamine before and after L-NNA, respectively). In contrast, dobutamine-associated changes in CSF cAMP were unchanged by L-NNA (1,108 +/- 56 and 2,623 +/- 139 fmol/ml vs. 1,059 +/- 24 and 2,500 +/- 61 fmol/ml for control and 10(-6) M dobutamine before and after L-NNA, respectively). Salbutamol, a beta 2-agonist, and isoproterenol, a nonselective beta-agonist, elicited similar changes in pial diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also were similarly inhibited by L-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of PACAP in the relationship between cAMP and opioids in hypoxia-induced pial artery vasodilation

1997 ◽  
Vol 272 (3) ◽  
pp. H1350-H1358 ◽  
Author(s):  
M. J. Wilderman ◽  
W. M. Armstead
Keyword(s):  
Adenylate Cyclase ◽  
Statistical Tests ◽  
Severe Hypoxia ◽  
Methionine Enkephalin ◽  
Pial Artery ◽  
Pituitary Adenylate Cyclase ◽  
Alpha Level ◽  
Before And After ◽  
The Relationship

The opioids methionine enkephalin and leucine enkephalin contribute to hypoxic pial artery dilation in the newborn pig, and adenosine 3',5'-cyclic monophosphate (cAMP) analogs have been shown to elevate cerebrospinal fluid (CSF) opioid concentration. The present study was designed to investigate the contribution of cAMP to hypoxic dilation and to determine whether an endogenous activator of adenylate cyclase, pituitary adenylate cyclase-activating peptide (PACAP), could modulate the cAMP-induced release of opioids to contribute to hypoxic pial dilation in piglets equipped with closed cranial windows. An alpha level of P < 0.05 was considered significant in all statistical tests. Moderate and severe hypoxia (PO2 approximately 35 and 25 mmHg, respectively) induced pial artery dilation that was attenuated by the Rp diastereomer of 8-bromoadenosine 3',5'-cyclic monophosphothioate (Rp-8-BrcAMPS), a cAMP antagonist (24 +/- 1 and 36 +/- 2% vs. 21 +/- 1 and 30 +/- 1% for moderate hypoxia and 34 +/- 1 and 46 +/- 2% vs. 24 +/- 1 and 32 +/- 1% for severe hypoxia before and after Rp-8-BrcAMPS, respectively). These responses were associated with an increased CSF cAMP (1,046 +/- 25, 1,366 +/- 28, and 1,735 +/- 47 fmol/ml for control, moderate, and severe hypoxia, respectively). Hypoxic pial dilation was also accompanied by an increase in CSF methionine enkephalin (1,101 +/- 62, 3,283 +/- 119, and 3,835 +/- 129 pg/ml for control, moderate, and severe hypoxia, respectively). Hypoxic dilation additionally increased CSF PACAP (1,727 +/- 86, 2,268 +/- 157, and 7,980 +/- 238 pg/ml for control, moderate, and severe hypoxia, respectively). PACAP (10(-8) and 10(-6) M) elicited pial dilation that was associated with increased CSF cAMP and blunted by Rp-8-BrcAMPS. PACAP-induced dilation was also accompanied by increases in the opioid methionine enkephalin (1,059 +/- 23, 1,483 +/- 34, and 2,108 +/- 77 pg/ml for control and 10(-8) and 10(-6) M PACAP, respectively). These data show that cAMP contributes to hypoxic pial artery dilation. Hypoxia increases CSF PACAP, whereas PACAP elevates CSF opioid concentration. These data, therefore, suggest that PACAP modulates cAMP-induced opioid release, thereby contributing to hypoxic pial dilation.

scholarly journals Role of Nitric Oxide, Cyclic Nucleotides, and the Activation of ATP-Sensitive K+ Channels in the Contribution of Adenosine to Hypoxia-Induced Pial Artery Dilation

1997 ◽  
Vol 17 (1) ◽  
pp. 100-108 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Cyclic Nucleotides ◽  
Severe Hypoxia ◽  
Similar Data ◽  
Adenosine Receptor Antagonist ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Synthase Inhibitor

Previously, it had been observed that nitric oxide (NO) contributes to hypoxia-induced pial artery dilation in the newborn pig. Additionally, it was also noted that activation of ATP-sensitive K+ channels (KATP) contribute to cGMP-mediated as well as to hypoxia-induced pial dilation. Although somewhat controversial, adenosine is also thought to contribute to hypoxic cerebrovasodilation. The present study was designed to investigate the role of NO, cyclic nucleotides, and activation of KATP channels in the elicitation of adenosine's vascular response and relate these mechanisms to the contribution of adenosine to hypoxia-induced pial artery dilation. The closed cranial window technique was used to measure pial diameter in newborn pigs. Hypoxia-induced artery dilation was attenuated during moderate (PaO2 ≈ 35 mm Hg) and severe hypoxia (PaO2 ≈ 25 mm Hg) by the adenosine receptor antagonist 8-phenyltheophylline (8-PT) (10–5 M) (26 ± 2 vs. 19 ± 2 and 34 ± 2 vs. 22 ± 2% for moderate and severe hypoxia in the absence vs. presence of 8-PT, respectively). This concentration of 8-PT blocked pial dilation in response to adenosine (8 ± 2, 16 ± 2, and 23 ± 2 vs. 2 ± 2, 4 ± 2, and 6 ± 2% for 10–8, 10–6, and 10–4 M adenosine before and after 8-PT, respectively). Similar data were also obtained using adenosine deaminase as a probe for the role of adenosine in hypoxic pial dilation. Adenosine-induced dilation was associated with increased CSF cGMP concentration (390 ± 11 and 811 ± 119 fmol/ml for control and 10–4 M adenosine, respectively). The NO synthase inhibitor, L-NNA, and the cGMP antagonist, Rp 8-bromo cGMPs, blunted adenosine-induced pial dilation (8 ± 1, 14 ± 1, and 20 ± 3 vs. 3 ± 1, 5 ± 1, and 8 ± 3% for 10–8, 10–6, and 10–4 M adenosine before and after L-NNA, respectively). Adenosine dilation was also blunted by glibenclamide, a KATP antagonist (9 ± 2, 14 ± 3, 21 ± 4 vs. 4 ± 1, 8 ± 2, and 11 ± 2% for 10–8, 10–6, and 10–4 M adenosine before and after glibenclamide, respectively). Finally, it was also observed that adenosine-induced dilation was associated with increased CSF cAMP concentration and the cAMP antagonist, Rp 8-bromo cAMPs, blunted adenosine pial dilation. These data show that adenosine contributes to hypoxic pial dilation. These data also show that NO, cGMP, cAMP, and activation of KATP channels all contribute to adenosine induced pial dilation. Finally, these data suggest that adenosine contributes to hypoxia-induced pial artery dilation via cAMP and activation of KATP channels by NO and cGMP.

Relationship between vasopressin and opioids in hypoxia induced pial artery vasodilation

1996 ◽  
Vol 271 (2) ◽  
pp. H521-H527 ◽  
Author(s):  
M. I. Rossberg ◽  
W. M. Armstead
Keyword(s):  
Receptor Antagonist ◽  
Severe Hypoxia ◽  
Vasopressin Receptor ◽  
Fetal Sheep ◽  
Moderate Hypoxia ◽  
Cranial Window ◽  
Pial Artery ◽  
Window Technique ◽  
Vasopressin Receptor Antagonist ◽  
And Control

It has been observed that a vasopressin receptor antagonist attenuates hypoxic hyperemia in fetal sheep, whereas methionine enkephalin (Met) and leucine enkephalin (Leu) contribute to hypoxia-induced pial artery dilation in newborn pigs. This study was designed to investigate the relationship between vasopressin and opioids in hypoxia-induced pial artery dilation in the newborn pig by use of the closed cranial window technique. Hypoxia-induced pial artery dilation was attenuated during moderate [arterial Po2 (PaO2) approximately 35 mmHg] and severe hypoxia (PaO2 approximately 25 mmHg) by the vasopressin receptor antagonist, [beta-mercapto-beta beta-cyclopentamethylenepropionyl, 2-O-Me-Tyr2, Arg8]vasopressin (MeAVP, 5 micrograms/kg i.v.; 29 +/- 1 vs. 14 +/- 2 and 37 +/- 2 vs. 18 +/- 2% for moderate and severe hypoxia in absence vs. presence of MeAVP, respectively, n = 7). Hypoxia-induced dilation was accompanied by increased cerebrospinal fluid (CSF) vasopressin concentration (26 +/- 1 vs. 67 +/- 4 and 26 +/- 1 vs. 99 +/- 4 pg/ml for control vs. moderate and control vs. severe hypoxia, n = 5). Vasopressin increased CSF Met (895 +/- 28, 1,147 +/- 63, 1,327 +/- 48, and 1,600 +/- 75 pg/ml for control and 40, 400, and 4,000 pg/ml vasopressin, respectively, n = 7). CSF Leu concentration was similarly increased by vasopressin. Furthermore, MeAVP attenuated the release of Met during moderate hypoxia (910 +/- 38 and 2,682 +/- 49 vs. 911 +/- 38 and 2,110 +/- 84 pg/ml for control and moderate hypoxia in absence and presence of MeAVP, respectively, n = 5). MeAVP had similar effects on hypoxia-induced Leu release. These data show that vasopressin contributes to hypoxia-induced pial artery dilation and that vasopressin increases CSF Met and Leu concentrations. These data also suggest that elevated CSF vasopressin concentrations that occur during hypoxemia result in opioid release, which subsequently contributes to hypoxic pial artery dilation.

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