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Biomedical subjects

W M Armstead

Publications and source records attributed to W M Armstead.

At least 91 records · Page 5Linked to original sources
PubMed1994

Indomethacin reduces ischemia-induced alteration of blood-brain barrier transport in piglets.

Cerebral ischemia-reperfusion (Isc-Rep) alters blood-brain barrier (BBB) transport properties in piglets. Pretreatment with superoxide dismutase and catalase partially attenuates these effects. Activated O2 species produced with Isc-Rep in piglets are generated via prostaglandin (PG) H synthase. This experiment determines if products of PGH synthase alter BBB transport of sodium and albumin. Piglets anesthetized with nitrous oxide and halothane were divided into four groups: 1) control, 2) indomethacin (5 mg/kg iv) with no Isc-Rep, 3) Isc-Rep alone, and 4) Isc-Rep after pretreatment with indomethacin (Indo). Regional transfer coefficients (Kin) and regional cerebral blood flow (microspheres) were measured at 2 h reperfusion after 20 min total global cerebral ischemia. Kin values are represented as absolute values and also relative to blood flow to account for any changes in perfusion caused by ischemia and/or Indo. Indo alone did not alter sodium or albumin transfer compared with control animals. Isc-Rep alone caused a significant increase in sodium and albumin transport compared with all other groups (control cerebral sodium Kin was 18.2 +/- 2.7 cm3.g-1.s-1.10(6) vs. 32.9 +/- 3.1 for Isc-Rep, P < 0.05). In contrast, there was no significant difference in sodium or albumin transfer with Isc-Rep after Indo pretreatment (e.g., cerebral sodium Kin was 22.0 +/- 2.0 for Isc-Rep after Indo) compared with the control or Indo alone groups. Indo pretreatment effectively attenuates increased BBB transport of both sodium and albumin following cerebral ischemia. We conclude that products of PGH synthase are involved in BBB alterations of protein and cation transport that follow the early stages of cerebral reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Transforming growth factor-beta attenuates ischemia-induced alterations in cerebrovascular responses.

We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Effects of indomethacin on newborn pig pial arteriolar responses to PCO2.

The present experiments were designed to determine whether hypocapnic cerebral vasoconstriction, like hypercapnic dilation, involves prostanoids and, if not, whether alternative mechanisms are related to the absolute arterial PCO2 (PaCO2) or the direction of change. We determined effects of indomethacin (5 mg/kg iv) on pial arteriolar responses to 1) increased PCO2 from normal, 2) decreased PCO2 from normal, and 3) increased PCO2 from hypocapnia to normocapnia in anesthetized newborn pigs. Pial arterioles constricted in response to hypocapnia (PaCO2 = 15-24 Torr) similarly before (-13 +/- 3%) and after (-16 +/- 2%) indomethacin. Cortical periarachnoid cerebrospinal fluid prostanoids were not increased by hypocapnia. As previously reported, cerebral vascular responses to hypercapnia (which increases cerebrospinal fluid prostanoids) were lost after indomethacin. To determine whether the failure of indomethacin to affect the responses to hypocapnia was due to the direction of change (decreasing) or the absolute level of PCO2, piglets were hyperventilated to approximately 15 Torr PaCO2. Increasing PaCO2 in these piglets to approximately 44 Torr caused pial arteriolar dilation (46 +/- 7%) that was not blocked by indomethacin (33 +/- 5%). Cortical periarachnoid prostanoids were not altered when PaCO2 was raised from hypocapnia to normocapnia. Therefore the relationship between CO2 and piglet cerebral vascular tone appears to involve multiple mechanisms. Specifically, dilation in response to CO2 above the normal range appears to involve prostanoids but changes in pial arteriolar diameter at low PaCO2 do not.

Animals↗
PubMed1993

Superoxide scavengers do not prevent ischemia-induced alteration of cerebral vasodilation in piglets.

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Effects of indomethacin on cerebral vasodilator responses to arachidonic acid and hypercapnia in newborn pigs.

Responses of pial arterioles to topically applied arachidonic acid, conversion of exogenous arachidonic acid to prostanoids, and pial arteriolar dilation to hypercapnia were examined before and at progressive times after treatment with indomethacin (5 mg/kg i.v.) in chloralose-anesthetized newborn pigs with closed cranial windows. Before treatment with indomethacin, arachidonic acid and hypercapnia dilated pial arterioles and increased cortical periarachnoid cerebrospinal fluid concentrations of 6-keto-prostaglandin (PG) F1 alpha and PGE2. One h after indomethacin treatment, the dilations and prostanoid synthesis were blocked. By 2 h after indomethacin treatment, hypercapnia produced significant dilation of pial arterioles, and dilation to both stimuli had returned to preindomethacin levels by 3 h. Inhibition of conversion of exogenous arachidonic acid to prostanoids as monitored by increases in 6-keto-PGF1 alpha and PGE2 in cerebrospinal fluid under the window also was reversed by 3 h after treatment with indomethacin. Repeated indomethacin treatment again blocked dilations and conversion of arachidonic acid to prostanoids on the brain surface. The possibility of short duration of vascular effectiveness of indomethacin when it is administered systemically needs to be considered, both when it is used as a probe for understanding contributions of PGH synthase products to control of cerebral circulation and when it is used therapeutically in attempts to alter the newborn cerebral circulation.

Animals↗
PubMed1993

Pituitary adenylate cyclase-activating polypeptide dilates cerebral arterioles of newborn pigs.

The actions of the 38- and 27-amino acid forms of synthetic pituitary adenylate cyclase-activating polypeptide (PACAP-38 and PACAP-27) on cerebral arterioles were tested in anesthetized newborn pigs equipped with closed cranial windows. The diameter changes of pial arterioles to topical PACAP were measured and cortical periarachnoid cerebrospinal fluid samples were collected for measurement of cAMP. The 38- and 27-amino acid forms of PACAP produced similar dose-dependent vasodilations. The increases of pial arteriolar diameter produced by PACAP-38 were 6 +/- 1%, 15 +/- 2%, 23 +/- 3%, and 38 +/- 3%, and those produced by PACAP-27 were 6 +/- 1%, 15 +/- 2%, 27 +/- 5%, and 38 +/- 8% at 10((-9), 10(-8), 10(-7), and 10(-6) M, respectively. Arteriolar diameter began to increase 1-2 min and reached a maximum 6-8 min after topical application of PACAP. Vasoactive concentrations of PACAP-38 and PACAP-27 increased cerebrospinal fluid cAMP levels dose dependently. Thus, PACAP-38 and PACAP-27 appear to stimulate cerebral adenylate cyclase and are potent dilators of newborn pigs pial arterioles.

Animals↗
PubMed1992

The influence of opioids on local cerebral glucose utilization in the newborn pig.

Topical methionine enkephalin, leucine enkephalin, and dynorphin (10(-6)M) previously have been observed to produce prominent pial arteriolar dilation. Dilation to these opioids could be caused directly by opioids acting on vascular receptors, or indirectly, as a consequence of increased metabolism. Therefore, we examined this possibility by determining the influence of opioids on cerebral glucose utilization in piglets with closed cranial windows using the [14C]deoxyglucose method. Qualitatively, the autoradiographic images expressed as a change in relative optical density from vehicle were unchanged by these opioids. Quantitatively, the opioids similarly had no effect on cerebral glucose utilization (53 +/- 5, 70 +/- 8, 63 +/- 5, and 52 +/- 3, mumol.100 g-1.min-1 for vehicle, methionine enkephalin, leucine enkephalin, and dynorphin, respectively). In contrast, topical glutamate (10(-3) M) produced similar dilation but increased cerebral glucose utilization (41 +/- 3 vs 89 +/- 8 mumol.100 g-1.min-1 for vehicle and glutamate, respectively). Therefore, these opioids do not appear to produce vascular effects through a change in cerebral metabolic utilization of glucose.

Animals↗
PubMed1992

Influence of opioids on CSF vasopressin concentration in newborn pigs.

This study was designed to determine the influence of opioids on periarachnoid cortical cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs equipped with closed cranial windows. Topical dynorphin-(1-13) produced tone-dependent pial arterial responses (dilation during normotension, constriction when cerebrovascular tone was decreased by hypotension). Dynorphin-(1-13) increased periarachnoid cortical CSF vasopressin concentrations in both normotensive and hypotensive piglets (5 +/- 1, 11 +/- 1, and 233 +/- 27 microU/ml for control, 10(-10), and 10(-6) M dynorphin-(1-13) during normotension, respectively). Dynorphin-(1-8) and U 50488H, a purported selective kappa-opioid receptor agonist, produced similar tone-dependent responses associated with smaller increases in CSF vasopressin concentration. beta-Endorphin caused only cerebral vasoconstriction associated with modest increases in CSF vasopressin (3 +/- 1, 5 +/- 1, 9 +/- 2 microU/ml for control, 10(-10), and 10(-6) M beta-endorphin, respectively). In contrast, methionine enkephalin- and leucine enkephalin-induced dilations were not associated with changes in CSF vasopressin concentration. Naloxone (1 mg/kg i.v.) blocked both the opioid-induced vascular effects and associated changes in CSF vasopressin concentration. Naloxone also attenuated the increase in CSF vasopressin concentration in response to hemorrhagic hypotension. These data show that dynorphin- and beta-endorphin-induced cerebrovascular effects are associated with increased CSF vasopressin concentration. Furthermore, these data indicate that opioids could contribute to the increase in CSF vasopressin concentration observed in response to hemorrhagic hypotension.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Topical arachidonic acid restores pial arteriolar dilation to hypercapnia of postischemic newborn pig brain.

In the newborn pig, cerebral vasodilator responses to hypercapnia are lost after cerebral ischemia. We examined the effect of topical application of arachidonic acid (30 micrograms/ml, 20 min) to the postischemic piglet brain on subsequent pial arteriolar dilated in response to hypercapnia (10% CO2 ventilation) and topical isoproterenol (10(-6), 10(-7) M). After 20 min cerebral ischemia, pial arterioles did not dilate to hypercapnia but responded to isoproterenol in a fashion similar to before ischemia. Treatment with arachidonic acid after ischemia restored pial arteriolar dilation to hypercapnia. Hypercapnia caused an increase in cortical periarachnoid concentration of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) before but not after ischemia. After postischemic treatment with arachidonic acid, the increase in cortical periarachnoid fluid 6-keto-PGF1 alpha during hypercapnia was restored. Therefore, topical application of arachidonic acid to cerebral vessels restores cerebral prostanoid synthesis and pial arteriolar dilation in response to hypercapnia that has been abolished by ischemia.

Administration, Topical↗
PubMed1992

Prostanoids modulate opioid-induced increases in cerebrospinal fluid vasopressin concentration.

Topical dynorphin and beta-endorphin produce increases in both prostanoid and vasopressin concentrations in cortical periarachnoid fluid of newborn pigs. The present study, in anesthetized piglets with cranial windows implanted, investigated the role of these prostanoids in the mediation of this vasopressin release by opioids. Topical prostaglandin (PG) I2 (100 ng/ml) increased pial arteriolar diameter from 145 +/- 4 to 178 +/- 4 microns and also increased cerebrospinal fluid (CSF) vasopressin from 1.1 +/- 0.1 to 4.1 +/- 0.5 microU/ml, but CSF vasopressin was not changed by PGE2, PGF2 alpha, and U-46619. Therefore, it is possible that PGI2 causes the increase in CSF vasopressin produced by opioids. Consistent with this concept, indomethacin and aspirin blocked dynorphin- and beta-endorphin-induced vasopressin release. The present data indicate that PGI2 contributes to opioid-induced changes in CSF vasopressin concentration and, thereby, to vasopressinergic contributions to opioid-induced cerebral vascular responses.

Animals↗
PubMed1992

Cerebral vasoconstriction in response to hypocapnia is maintained after ischemia/reperfusion injury in newborn pigs.

BACKGROUND AND PURPOSE: Hypocapnic cerebral vasoconstriction is used therapeutically to reduce elevated intracranial pressure caused by cerebral edema. Because cerebral ischemia/reperfusion injury causes a selective loss of prostanoid-dependent responses, including vasodilation to hypercapnia, we designed these experiments to examine the effect of ischemia/reperfusion on hypocapnic cerebral vasoconstriction. METHODS: Microvascular responses were studied in 10 newborn pigs (closed cranial window) in response to hyperventilation-induced hypocapnia (PaCO2, 22 +/- 2 mm Hg) both before and 45 minutes after 20 minutes of global cerebral ischemia. Responses to hypercapnia (PaCO2, 63 +/- 3 mm Hg), topical isoproterenol (10(-7) M), and norepinephrine (10(-4) M) were also studied before and after ischemia in the same animals for comparison. RESULTS: Before ischemia/reperfusion, pial arterioles vasoconstricted to hypocapnia (-17 +/- 2%) and norepinephrine (-35 +/- 4%) and vasodilated to CO2 (37 +/- 7%) and isoproterenol (25 +/- 2%). After ischemia/reperfusion, the constriction of pial arterioles to hypocapnia (-19 +/- 2%) was similar to that before ischemia. This is in contrast to the loss of dilation to hypercapnia. Dilation to isoproterenol and constriction to norepinephrine were not affected by ischemia. CONCLUSIONS: Hypocapnic cerebral vasoconstriction is maintained after ischemia/reperfusion. Since prostanoid-dependent responses, such as hypercapnic dilation, are lost following cerebral ischemia, these data suggest that hypocapnic constriction is not dependent on an intact prostanoid system and that cerebral vascular responses to CO2 involve multiple mechanisms, depending on whether CO2 is increasing or decreasing from baseline.

Animals↗
PubMed1992

Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets.

BACKGROUND AND PURPOSE: Transport of urea across the blood-brain barrier is increased during postischemic cerebral reperfusion in the piglet. Ischemia/reperfusion also has been observed to increase apparent superoxide anion generation on the surface of the brain. The present study was designed to address the hypothesis that the increased transfer of urea into the brain after ischemia/reperfusion could be due to superoxide anion-induced alterations in blood-brain barrier permeability. METHODS: Blood-to-brain transfer of carbon-14-labeled urea was measured in four groups (n = 7 each) of newborn pigs: 1) control (no ischemia, no pretreatment), 2) pretreatment with polyethylene glycol superoxide dismutase (1,000 IU/kg) and polyethylene glycol catalase (10,000 IU/kg i.v.) but no ischemia, 3) no pretreatment and 20 minutes of ischemia followed by 2 hours of reperfusion, and 4) pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase in addition to ischemia/reperfusion. The following brain regions were investigated: cerebrum, caudate, midbrain, pons, medulla, and cerebellum. RESULTS: Polyethylene glycol superoxide dismutase inhibited generation of superoxide anion by the brain during reperfusion after ischemia. Regional transfer of [14C]urea from blood to brain increased at 2 hours' reperfusion. This ischemia-induced increase in blood-to-brain transfer of [14C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kin was 28 +/- 2 in the control group, 26 +/- 3 in the pretreated/no ischemia group, 67 +/- 5 in the untreated/ischemia group, and 40 +/- 2 ml.g-1.s-1.10(6) in the pretreated/ischemia group. After ischemia/reperfusion, cerebral blood flow was unchanged by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase. CONCLUSIONS: These data suggest that production of a partially reduced species of oxygen contributes to the increased urea transfer across the blood-brain barrier after ischemia in the newborn pig.

Animals↗
PubMed1992

Alterations in cerebrovascular reactivity after positive pressure ventilation.

Pressure ventilation of the newborn can adversely affect the cardiovascular system. Increasing airway pressure increases cerebral venous pressure, thus stressing brain vasculature. To test the hypothesis that cerebral venous distension caused by mechanical ventilation alters cerebral microvascular responses, we studied cerebrovascular responses before, during, and after positive pressure ventilation. Anesthetized newborn pigs were ventilated with a standard time-cycled, pressure-limited infant respirator. Pial arterioles were measured in response to hypercapnia, topical isoproterenol, and topical norepinephrine during control [mean airway pressure (Paw) = 0.9 +/- 0.05 kPa (4.8 +/- 0.3 cm H2O)] conditions, during 40-60 min of increased Paw [2.5 +/- 0.2 kPa (13.9 +/- 1.3 cm H2O)], and when the Paw was lowered again. Pial arteriolar dilation in response to hypercapnia was not changed by increasing Paw. Similarly, responses to isoproterenol and norepinephrine were unaltered during raised Paw. However, a significant decrease in responses to topical isoproterenol and norepinephrine was observed after increased Paw. These experiments show that specific prostanoid-independent cerebrovascular responses are altered subsequent to pressure ventilation, whereas prostanoid-dependent dilation to hypercapnia was not affected. These changes suggest that the newborn cerebral vasculature is affected by positive pressure ventilation, further raising the possibility that ventilation-induced alterations in microvascular responses could make the brain more vulnerable to added stresses after pressure ventilation.

Animals↗
PubMed1992

Vasopressin modulates cerebrovascular responses to opioids in newborn pigs.

Vasopressin receptor blockade has been observed to attenuate the systemic vascular effects of dynorphin. This study was designed to determine the ability of vasopressin to modulate cerebrovascular responses to opioids in newborn pigs equipped with closed cranial windows. Topical dynorphin 13 increased pial arteriolar diameter during normotension (151 +/- 5, 171 +/- 4, 183 +/- 4 and 187 +/- 4 microns for control, 10(-10), 10(-8) and 10(-6) M dynorphin 13, respectively). During hypotension, however, responses to dynorphin 13 were reversed to concentration-dependent decreases in pial arteriolar diameter (184 +/- 3, 169 +/- 4, 165 +/- 4 and 159 +/- 4 microns for control 10(-10), 10(-8) and 10(-6) M dynorphin 13, respectively). Dynorphin 13-induced pial arteriolar dilation was potentiated by the V1 receptor antagonist [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid) 2(o-methyl)-Tyr-AVP] (MEAVP; 5 micrograms/kg i.v.; 14 +/- 1, 22 +/- 1 and 24 +/- 1% vs. 19 +/- 1, 26 +/- 1 and 30 +/- 1% increase for 10(-10), 10(-8) and 10(-6) M dynorphin 13 before and after MEAVP, respectively). In contrast, dynorphin 13-induced constriction during hypotension was markedly reduced by MEAVP (10 +/- 1, 15 +/- 1 and 16 +/- 2% vs. 1 +/- 1, 4 +/- 1 and 9 +/- 1% decrease for 10(-10), 10(-8) and 10(-6) dynorphin 13 before and after MEAVP, respectively). Dynorphin 8 and the synthetic kappa-opioid selective agonist, U5O,488H, elicited similar tone-dependent responses that were modified by MEAVP in a similar fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Effects of ischemia/reperfusion on brain tissue prostanoids and leukotrienes in newborn pigs.

We investigated the hypothesis that cerebral prostanoid and peptidoleukotriene (LTs) (LTC4/D4/E4/F4) synthesis are increased during postischemic reperfusion of newborn pig brains. Prostanoids and LTs extracted from brain tissue were determined by RIA in sham-control piglets and at 1h, 3h, or 12h after a 20-min period of total cerebral ischemia. During reperfusion following ischemia, all regional brain tissue (cerebrum, brain stem and cerebellum) prostanoids (6-keto-PGF1 alpha, TXB2, PGE2 and PGF2 alpha) were increased at 1h compared with those in sham-control piglets. Only cerebral and brain stem 6-keto-PGF1 alpha and cerebral TXB2 remained elevated at 3h postischemia and all prostanoids returned to control levels by 12h postischemia. Brain tissue LTs were lower than prostanoids and were not altered 1, 3, or 12h following ischemia. These data indicate that 1) newborn pig brain tissue prostanoids are increased initially, and then returned to control levels at later stages of reperfusion following ischemia; 2) LTs are present in newborn pig brain tissue, but are not increased by ischemia/reperfusion injury and therefore probably do not play a significant role in cerebral ischemia-reperfusion injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Opioids and the prostanoid system in the control of cerebral blood flow in hypotensive piglets.

The interaction between opioid and prostanoid mechanisms in the control of cerebral hemodynamics was investigated in the conscious hypotensive piglet. Radiomicrospheres were used to determine regional cerebral blood flow (rCBF) in piglets pretreated with the opioid receptor antagonist, naloxone, or its vehicle, saline, during normotension, hypotension, and after the administration of indomethacin, a cyclooxygenase inhibitor, during hypotension. Hemorrhage (30 ml/kg) decreased systemic arterial pressure from 68 +/- 12 to 40 +/- 10 mm Hg but did not decrease blood flow to any brain region. Indomethacin treatment (5 mg/kg) of hypotensive piglets decreased blood flow to all brain regions within 20 min; this decrease in CBF resulted from increases in cerebral vascular resistance of 65 and 281% at 20 and 40 min after treatment, respectively. In hypotensive piglets, cerebral oxygen consumption was reduced from 2.62 +/- 0.71 to 0.53 +/- 0.27 ml 100 g-1 min-1 and to 0.11 +/- 0.04 ml 100 g-1 min-1 at 20 and 40 min following indomethacin, respectively. Treatment with naloxone (1 mg/kg) had no effect on rCBF, calculated cerebral vascular resistance, or cerebral oxygen consumption of normotensive or hypotensive piglets. However, decreases in CBF and oxygen consumption and increases in cerebral vascular resistance upon treatment of hypotensive piglets with indomethacin were attenuated in animals pretreated with naloxone. These data indicate that the removal of prostanoid modulation of an opioid-mediated constrictor influence on the cerebral circulation is a potential mechanism for the increase in cerebral vascular resistance that follows indomethacin treatment of hypotensive piglets.

Animals↗
PubMed1991

Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs.

In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation.

Animals↗