Prostanoids modulate opioid-induced increases in cerebrospinal fluid vasopressin concentration

1992 ◽  
Vol 263 (6) ◽  
pp. H1670-H1674
Author(s):  
W. M. Armstead ◽  
R. Mirro ◽  
M. Shibata ◽  
C. W. Leffler
Keyword(s):  
Cerebrospinal Fluid ◽  
Vasopressin Release ◽  
Vascular Responses ◽  
Beta Endorphin ◽  
Newborn Pigs ◽  
Induced Changes ◽  
Arteriolar Diameter ◽  
Cerebral Vascular

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.

Cerebral arteriolar dilation to hypoxia: role of prostanoids

1997 ◽  
Vol 272 (1) ◽  
pp. H418-H424 ◽  
Author(s):  
C. W. Leffler ◽  
H. Parfenova
Keyword(s):  
Cerebrospinal Fluid ◽  
Rapid Decrease ◽  
Primary Mechanism ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
Cerebral Vasodilation ◽  
Arteriolar Diameter ◽  
Indomethacin Treatment

Experiments addressed the hypothesis that dilator prostanoids contribute to maintenance of low cerebral microvascular tone during hypoxia in the newborn. Anesthetized newborn pigs equipped with closed cranial windows were used to measure responses of pial arterioles (approximately 60 microns) to treatments. Hypoxia (Pao2 approximately equal to 25 mmHg) caused dilation of pial arterioles (approximately 50% increase in diameter). Hypoxia (5 min) caused an increase in cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha concentration from 907 +/- 171 (normoxia) to 1,408 +/- 213 pg/ml (hypoxia). Pretreatment with indomethacin (5 mg/kg) did not affect pial arteriolar dilation to hypoxia. Conversely, indomethacin treatment during hypoxia caused a rapid decrease in arteriolar diameter to nearly the normoxia diameter within 3 min, returning to the original hypoxia diameter by 10 min. Ibuprofen treatment (30 mg/kg) had no effect on pial arteriolar diameter during normoxia or hypoxia, and pretreatment did not alter dilation to hypoxia. However, pretreatment with ibuprofen abolished the constrictor effect of indomethacin given during hypoxia. These data suggest that the primary mechanism by which hypoxia produces cerebral vasodilation does not involve prostanoids, but prostanoids can contribute to cerebral vasodilation in response to hypoxia.

Lipoxins A4 and B4 dilate cerebral arterioles of newborn pigs

1989 ◽  
Vol 256 (2) ◽  
pp. H468-H471 ◽  
Author(s):  
D. W. Busija ◽  
W. Armstead ◽  
C. W. Leffler ◽  
R. Mirro
Keyword(s):  
Cerebrospinal Fluid ◽  
Topical Application ◽  
Cerebral Microcirculation ◽  
Lipoxin A4 ◽  
Vascular Responses ◽  
Neonatal Pigs ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
Newborn Pigs ◽  
Arteriolar Diameter

We determined the effects of lipoxins A4 and B4 on the cerebral microcirculation of neonatal pigs and whether vascular responses were modulated by prostanoids. Pial arteriolar diameters were determined using a closed cranial window and intravital microscopy. Before lipoxin A4 application, arteriolar diameter was 143 +/- 6 microns (means +/- SE). Topical application of lipoxin A4 increased the diameter to 160 +/- 7 microns at 0.1 ng/ml, 167 +/- 7 microns at 1 ng/ml, and 173 +/- 7 microns at 10 ng/ml (n = 9). Before application of lipoxin B4, arteriolar diameter was 146 +/- 7 microns. Topical application of lipoxin B4 increased the diameter to 165 +/- 7, 169 +/- 6, and 175 +/- 6 microns at 0.1, 1, and 10 ng/ml (n = 9), respectively. Intravenous injection of indomethacin (5 mg/kg) or vehicle did not affect these responses. Levels of prostaglandins E2 and F2 alpha in cerebrospinal fluid (measured by radioimmunoassay) did not increase in response to lipoxins. We conclude that lipoxins are dilator stimuli in the cerebral circulation and that prostanoids do not mediate these responses.

Effects of indomethacin on newborn pig pial arteriolar responses to PCO2

1993 ◽  
Vol 75 (3) ◽  
pp. 1300-1305 ◽  
Author(s):  
R. Mirro ◽  
L. J. Pharris ◽  
W. M. Armstead ◽  
M. Shibata ◽  
C. W. Leffler
Keyword(s):  
Cerebrospinal Fluid ◽  
Absolute Level ◽  
Arterial Pco2 ◽  
Cerebral Vasoconstriction ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
The Absolute ◽  
The Relationship ◽  
Arteriolar Diameter ◽  
Cerebral Vascular

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.

Cerebral ischemia alters cerebral microvascular reactivity in newborn pigs

1989 ◽  
Vol 257 (1) ◽  
pp. H266-H271 ◽  
Author(s):  
C. W. Leffler ◽  
D. G. Beasley ◽  
D. W. Busija
Keyword(s):  
Cerebrospinal Fluid ◽  
Cerebral Ischemia ◽  
Sham Control ◽  
Microvascular Reactivity ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
Pg E2 ◽  
Cerebral Vasodilator ◽  
Arteriolar Diameter ◽  
Prostanoid Synthesis

The effects of cerebral ischemia on cerebral microvascular reactivity and prostanoid synthesis were examined in chloralose-anesthetized newborn pigs. Microvascular responses and periarachnoid cerebrospinal fluid (CSF) prostanoid concentrations were determined between 10 and 140 min after a 20-min period of total cerebral ischemia, as well as in sham-control piglets without cerebral ischemia. After cerebral ischemia, the decrease in pial arteriolar diameter in response to topical norepinephrine (10(-4) M) was similar in sham (-27 +/- 6%) and postischemic (-25 +/- 5%) piglets. However, the increase in pial arteriolar diameter in response to hypercapnia (10% CO2 ventilation) that was observed in sham piglets (+21 +/- 5%) was absent after ischemia (-2 +/- 3%). In contrast, dilations of pial arterioles in response to topical prostaglandin (PG)E2 (at 100 ng PGE2/ml: sham, +13 +/- 3%; postischemia, +21 +/- 4%) and topical isoproterenol (10(-6) M) (sham, +29 +/- 4%; postischemia, +23 +/- 3%) were not decreased by prior cerebral ischemia. In sham piglets, norepinephrine and hypercapnia produced increases in cortical periarachnoid prostanoid concentrations, whereas after cerebral ischemia, neither stimulus increased cortical periarachnoid prostanoid concentrations. The results are consistent with the hypothesis that failure of hypercapnia to dilate pial arterioles after cerebral ischemia results from the inability of this stimulus to increase cerebral vasodilator prostanoid synthesis.

Prostanoids promote pial arteriolar dilation and mask constriction to oxytocin in piglets

1993 ◽  
Vol 264 (4) ◽  
pp. H1023-H1027
Author(s):  
D. W. Busija ◽  
I. Khreis ◽  
J. Chen
Keyword(s):  
Cerebrospinal Fluid ◽  
Intravital Microscopy ◽  
Prostaglandin Synthesis ◽  
Pial Arterioles ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Csf Levels ◽  
Low Levels ◽  
Arteriolar Diameter ◽  
Baseline Diameter

We determined effects of oxytocin on piglet pial arterioles and the role of prostanoids in mediating arteriolar responses. Anesthetized piglets were equipped with closed cranial windows, and arteriolar diameter was measured using intravital microscopy. Pial arterioles were exposed to 10(-10) to 10(-4) M oxytocin. Cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were determined using radioimmunoassay. Baseline diameter was 110 +/- 4 microns and increased to 120 +/- 6 microns at 10(-8) M (9 +/- 3%, n = 20). CSF levels of PGE2 were 697 pg/ml during baseline and increased to 1,685 +/- 316 pg/ml during 10(-6) M, 2,243 +/- 327 pg/ml during 10(-5) M, and 2,941 +/- 500 pg/ml during 10(-4) (n = 6). CSF levels of 6-keto-PGF1 alpha were 354 +/- 73 pg/ml during baseline and increased to 734 +/- 168 pg/ml at 10(-5) M and to 836 +/- 167 pg/ml at 10(-4) M (n = 5). After inhibition of prostaglandin synthesis by indomethacin (5 mg/kg i.v.), oxytocin constricted at all doses, starting at 10(-10) M (5 +/- 2%) and continuing to constrict at 10(-4) M (24 +/- 2%, n = 14). We conclude that: 1) piglet pial arterioles respond to relatively low levels of oxytocin, 2) local presence and/or production of prostanoids promotes dilation, and 3) endogenous prostanoids prevent constriction of pial arterioles to oxytocin. Our results suggest that oxytocin could play a role in the regulation of cerebral hemodynamics.

scholarly journals Different Pial Arteriolar Responses to Acetylcholine in the Newborn and Juvenile Pig

1994 ◽  
Vol 14 (6) ◽  
pp. 1088-1095 ◽  
Author(s):  
W. M. Armstead ◽  
S. L. Zuckerman ◽  
M. Shibata ◽  
H. Parfenova ◽  
C. W. Leffler
Keyword(s):  
Age Groups ◽  
Phosphodiesterase Inhibitor ◽  
Calcium Ionophore ◽  
Cranial Window ◽  
Window Technique ◽  
Newborn Pigs ◽  
Induced Changes ◽  
Arteriolar Diameter ◽  
Methyl Xanthine ◽  
Do So

Using the closed cranial window technique, the present study was designed to test the hypothesis that the pial arteriolar response to acetylcholine is age dependent. In newborn pigs (1–5 days old) pretreated with the phosphodiesterase inhibitor isobutyl methyl xanthine (IBMX), acetylcholine (10−5 M) produced pial arteriolar constriction with no change in CSF cyclic GMP (cGMP) that was blocked by indomethacin (5 mg/kg i.v.). In contrast, in indomethacin- and IBMX-treated juvenile pigs (3–4 weeks old), acetylcholine (10− M) increased the pial arteriolar diameter by 17 ± 1% and increased CSF cGMP by 2.1 ± 0.3-fold. Similar vascular and biochemical changes for acetylcholine were observed in juvenile pigs pretreated with only IBMX. In the absence of IBMX, acetylcholine produced modest pial constriction in juvenile pigs. In the IBMX-pretreated juvenile pigs, l-nitroarginine (LNA; 10−6 M) decreased pial arteriolar diameter by 15 ± 2% and blocked acetylcholine-induced dilation and associated changes in CSF cGMP. A23187, a calcium ionophore, and sodium nitroprusside (SNP) elicited similar dilation and changes in CSF cGMP in both age groups. LNA blocked A23187 dilation, but SNP dilation was unchanged. l-Arginine (10−3 M) partially restored acetylcholine- and A23187-induced dilation to indomethacin- and LNA-pretreated juvenile pigs. These data show that acetylcholine produces dilation in the juvenile pig through the production of the putative endothelium-derived relaxing factor (EDRF) nitric oxide but does not do so in the newborn period. We speculate that contributions of EDRF to the acetylcholine-induced changes in pial arteriolar diameter develop with age.

Cyclic nucleotides and cerebrovascular tone in newborn pigs

1993 ◽  
Vol 265 (6) ◽  
pp. H1972-H1982 ◽  
Author(s):  
H. Parfenova ◽  
M. Shibata ◽  
S. Zuckerman ◽  
R. Mirro ◽  
C. W. Leffler
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclic Nucleotides ◽  
Vascular Tone ◽  
Dibutyryl Camp ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
Camp And Cgmp ◽  
Arteriolar Diameter

Relationships between cyclic nucleotides and cerebrovascular tone were investigated using closed cranial windows in anesthetized newborn pigs. Pial arteriolar diameter was monitored and cerebrospinal fluid (CSF) was collected from beneath the cranial window. Adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) concentrations in CSF were 1,690 +/- 200 and 730 +/- 40 fmol/ml, respectively. Topically applied isozyme-selective and nonselective inhibitors [3-isobutyl-1-methylxanthine (IBMX), theophylline, Ro 201724, dipyridamole, zaprinast, calmidazolium, and W-7] of cyclic nucleotide phosphodiesterases dilated pial arterioles with concomitant increases in cAMP and/or cGMP levels in CSF. Topical application of dibutyryl-cAMP and dibutyryl-cGMP also resulted in pial arteriolar dilation. Ten-minute hypercapnia, which results in pial arteriolar dilation, increased cAMP to 5,240 +/- 900 and cGMP to 1,350 +/- 200 fmol/ml. IBMX and zaprinast potentiated the increases in cAMP and cGMP as well as the cerebrovascular dilation in response to hypercapnia. These data suggest that cyclic nucleotides contribute to regulation of cerebral vascular tone during control conditions. Furthermore, cAMP and/or cGMP appears to be involved in arterial vasodilation in response to hypercapnia in newborn pigs.

Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits

1991 ◽  
Vol 261 (4) ◽  
pp. R828-R834 ◽  
Author(s):  
M. Shibata ◽  
C. W. Leffler ◽  
D. W. Busija
Keyword(s):  
Cerebrospinal Fluid ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Brain Vessels ◽  
Cranial Window ◽  
Baseline Levels ◽  
Fluid Levels ◽  
The Brain ◽  
Arteriolar Diameter

The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD.

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