scholarly journals Effects of Dopamine on Pial Arteriolar Diameter and CSF Prostanoid Levels in Piglets

1989 ◽  
Vol 9 (3) ◽  
pp. 264-267 ◽  
Author(s):  
David W. Busija ◽  
Charles W. Leffler
Keyword(s):  
Topical Application ◽  
Intravital Microscopy ◽  
Prostaglandin E ◽  
Vascular Responses ◽  
Cranial Window ◽  
Window Technique ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
High Doses ◽  
Arteriolar Diameter

We examined effects of topically applied dopamine on pial arteriolar diameter and CSF prostanoid levels in newborn pigs. Vascular responses were determined using the closed cranial window technique and intravital microscopy, and prostanoids were determined by radioimmunoassay. Topical application of dopamine did not change arteriolar diameter at 10−7–10−5 M, but constricted arterioles at 10−4 (16%) and 10−3 M (30%). Intravenous administration of indomethacin (5 mg/kg) did not alter this constriction. In addition, CSF prostanoid levels did not increase in response to application of dopamine except for a modest increase of prostaglandin E2 at 10−3 M. We conclude that dopamine is a constrictor at high doses of piglet pial arterioles and that this response is not modified by endogenous prostanoids.

Altered cerebrovascular responsiveness to N-methyl-D-aspartate after asphyxia in piglets

1993 ◽  
Vol 265 (1) ◽  
pp. H389-H394 ◽  
Author(s):  
D. W. Busija ◽  
M. Wei
Keyword(s):  
Topical Application ◽  
Intravital Microscopy ◽  
Cranial Window ◽  
Time Control ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
Arteriolar Diameter ◽  
Baseline Diameter ◽  
H 30

We examined effects of prior asphyxia and reventilation on pial arteriolar responses to arterial hypercapnia, topical application of forskolin, and topical application of N-methyl-D-aspartate (NMDA) in newborn pigs. Piglets were anesthetized and ventilated with a respirator. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. After baseline diameter was determined, the respirator was turned off for 10 min. Then the respirator was turned on, and the piglet was ventilated for 4 h. At 1, 2, and 4 h after asphyxia, arteriolar diameter was determined during control conditions and during arterial hypercapnia (inspiration of 10% CO2 in air; n = 4), topical application of 2.4 x 10(-8) M forskolin (n = 6), and topical application of 10(-5) M NMDA (n = 6). At 1 h after asphyxia, arterial hypercapnia dilated pial arterioles by 39 +/- 3%, topical forskolin dilated pial arterioles by 24 +/- 3%, and NMDA dilated pial arterioles by 10 +/- 1%. For arterial hypercapnia and forskolin application, arteriolar responses were not different from 1 h at 2 and 4 h postasphyxia. In contrast, for NMDA, arteriolar responses were greater at 2 h (23 +/- 6%) and 4 h (30 +/- 5%) than at 1 h. In time-control animals, NMDA dilated arterioles by 20 +/- 5% at 1 h, by 24 +/- 8% at 2 h, and by 21 +/- 4% at 4 h (n = 5). Indomethacin administration (5 mg/kg iv) before asphyxia resulted in a 23 +/- 3% arteriolar dilation in response to NMDA at 1 h (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Dilator effects of amino acid neurotransmitters on piglet pial arterioles

1989 ◽  
Vol 257 (4) ◽  
pp. H1200-H1203 ◽  
Author(s):  
D. W. Busija ◽  
C. W. Leffler
Keyword(s):  
Amino Acids ◽  
Cranial Window ◽  
Window Technique ◽  
Prolonged Contact ◽  
Vascular Responsiveness ◽  
Pial Arterioles ◽  
Csf Levels ◽  
Newborn Pigs ◽  
Arteriolar Tone ◽  
Arteriolar Diameter

We examined the effects of topically applied amino acids (glutamate, aspartate, glycine, and taurine) and a synthetic glutamate analogue [N-methyl-D-aspartate (NMDA)] on pial arteriolar tone and cortical surface cerebrospinal fluid (CSF) dilator prostanoid concentrations in anesthetized newborn pigs. We also determined whether prolonged contact of pial arterioles with glutamate (10(-3) M) and aspartate (10(-3) M) would alter arteriolar responses to exogenous isoproterenol or norepinephrine. Vascular responses were determined using the closed cranial window technique and intravital microscopy. Concentrations of prostaglandin E2 and 6-ketoprostaglandin F1 alpha in CSF under the cranial window were determined using radioimmunoassay. At the highest dose tested (10(-3) M), NMDA dilated arterioles by 30 +/- 4% (n = 8), glutamate by 21 +/- 5% (n = 6), aspartate by 28 +/- 10% (n = 5), and taurine by 21 +/- 2% (n = 7). Glycine application did not change pial arteriolar diameter significantly (n = 8). The amino acids tested (NMDA and glutamate) did not increase CSF levels of dilator prostagnoids, and intravenous indomethacin trihydrate did not change vascular responsiveness to NMDA. Furthermore, dilator responsiveness to isoproterenol and constrictor responsiveness to norepinephrine were not affected significantly after 30 min of topical application of glutamate and aspartate to the pial surface (n = 4). We conclude that these amino acids are potent dilators of the neonatal cerebral circulation. The mechanism of dilation in the cases of NMDA and glutamate does not appear to involve dilator prostanoids. Furthermore, prolonged contact with excitatory amino acids under these conditions does not alter subsequent cerebrovascular responsiveness.

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.

Hypoglycemia selectively abolishes hypoxic reactivity of pial arterioles in piglets: role of adenosine

1995 ◽  
Vol 268 (2) ◽  
pp. H871-H878 ◽  
Author(s):  
T. S. Park ◽  
E. R. Gonzales ◽  
A. R. Shah ◽  
J. M. Gidday
Keyword(s):  
Arterial Pco2 ◽  
Adenosine Receptor Antagonist ◽  
Cranial Window ◽  
Newborn Piglets ◽  
Window Technique ◽  
Pial Arterioles ◽  
Cerebrovascular Regulation ◽  
Arterial Po2 ◽  
Arteriolar Diameter

Episodes of hypoxia often occur in hypoglycemic newborns, but it is not known whether dysfunctions in cerebrovascular regulation contribute to brain injury incurred by these affected neonates. We tested the hypotheses that 1) perinatal hypoglycemia impairs cerebrovascular responses to hypoxia and 2) a reduced vascular smooth muscle sensitivity to adenosine accounts for this impairment. Responses of 25- to 50-mu m-diam pial arterioles were determined using the cranial window technique in isoflurane-anesthetized newborn piglets < 5 days of age. Hypoxia (arterial PO2 = 28 +/- 1 mmHg) caused a 47 +/- 5% increase (P = 0.0008) in arteriolar diameter, 89% of which could be blocked by prior superfusion of the window space with the preferential A2-adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 50 microM). Insulin-induced hypoglycemia (blood glucose = 18 +/- 1 mg/dl without isoelectric electroencephalogram) caused a 31 +/- 5% increase (P = 0.002) in arteriolar diameter; however, no additional dilatative response to hypoxia (arterial PO2 = 28 +/- 1 mmHg) could be elicited in these animals. Arteriolar dilation of 41 +/- 6% (P = 0.002) induced by superfusion of 20 microM adenosine under normoglycemic conditions was also completely abolished after the animals were rendered hypoglycemic. Unlike the response to hypoxia and adenosine, hypoglycemia only attenuated prostanoid-dependent dilations to hypercapnia (arterial PCO2 = 68 +/- 3 mmHg) by 55 +/- 9%. These results indicate that, in the newborn, hypoglycemia selectively abolishes hypoxic reactivity through an impairment in adenosine-mediated cerebrovascular dilation.

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.

Influence of endothelin on piglet cerebral microcirculation

1989 ◽  
Vol 257 (2) ◽  
pp. H707-H710 ◽  
Author(s):  
W. M. Armstead ◽  
R. Mirro ◽  
C. W. Leffler ◽  
D. W. Busija
Keyword(s):  
Endothelial Cells ◽  
Cerebrospinal Fluid ◽  
Cerebral Microcirculation ◽  
Cranial Window ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Newborn Pigs ◽  
Fluid Levels ◽  
Porcine Endothelial Cells ◽  
Arteriolar Diameter

The purpose of this study was to determine responses of the newborn pig cerebral microcirculation to endothelin. Pial arterioles were observed directly using a closed cranial window in chloralose-anesthetized piglets. Topical application of endothelin derived from porcine endothelial cells produced increases in pial arteriolar diameter at the lowest concentration (0.1 ng/ml) (159 +/- 6 to 180 +/- 8 microns) and concentration-dependent decreases in pial arteriolar diameter at higher concentrations (141 +/- 6, 127 +/- 5, and 110 +/- 4 microns at 1, 10, and 100 ng/ml, respectively). Indomethacin (5 mg/kg iv) and aspirin (50 mg/kg iv) blocked dilator responses to endothelin and attenuated constrictor responses. Endothelin produced concentration-dependent increases in cortical periarachnoid cerebrospinal fluid levels of 6-ketoprostaglandin (6-keto-PG) F1 alpha, PGE2, PGF2 alpha, and thromboxane B2. Thus endothelin can produce either dilation or constriction of cerebral arterioles in newborn pigs, depending on concentration. Furthermore, prostanoids appear to mediate vasodilation induced by the lowest concentration of endothelin and contribute to constriction induced by higher concentrations of endothelin.

Prostanoids and pial arteriolar diameter in hypotensive newborn pigs

1987 ◽  
Vol 252 (4) ◽  
pp. H687-H691 ◽  
Author(s):  
C. W. Leffler ◽  
D. W. Busija
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Blood Flow ◽  
Prostaglandin E2 ◽  
Parietal Cortex ◽  
Topical Application ◽  
Thromboxane B2 ◽  
Pial Arterioles ◽  
Newborn Pigs ◽  
Arteriolar Diameter

Effects of hypotensive hemorrhage on pial arteriolar diameter and cortical subarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface (cortical subarachnoid CSF). Prostanoids in the CSF were determined by radioimmunoassay. Measurements of pial arterioles were made during normotension (63 +/- 4 mmHg) and hypotension (28 +/- 3 mmHg). Hypotension caused pial arteriolar diameters to increase from 162 +/- 22 to 193 +/- 22 microns. During normotension, the cortical subarachnoid prostanoid concentrations were (in ng/ml) prostaglandin E2 (PGE2) 2.6 +/- 0.7, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) 1.7 +/- 0.4, thromboxane B2 (TXB2) 0.25 +/- 0.02. Hypotension caused 6-keto-PGF1 alpha to increase 245 +/- 104% and PGE2 to increase 132 +/- 38%. TXB2 increased slightly (37 +/- 21%). Topical application of PGE2 and prostacyclin caused marked dilation of pial arterioles. Treatment of hypotensive newborn pigs with indomethacin caused constriction of pial arterioles to diameters not significantly different from the normotensive diameters. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow during hypotension in piglets.

scholarly journals Exogenous Norepinephrine Constricts Cerebral Arterioles via α2-Adrenoceptors in Newborn Pigs

1987 ◽  
Vol 7 (2) ◽  
pp. 184-188 ◽  
Author(s):  
David W. Busija ◽  
Charles W. Leffler
Keyword(s):  
Blood Brain Barrier ◽  
Topical Application ◽  
Intravenous Administration ◽  
Α2 Adrenoceptors ◽  
Neonatal Pigs ◽  
Cranial Window ◽  
Adrenoceptor Agonists ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Newborn Pigs

The purpose of this study was to determine whether exogenous norepinephrine mediates cerebrovascular constriction via α1- or α2-adrenoceptors in anesthetized neonatal pigs. Diameters of pial arterioles in anesthetized piglets, 1–6 days old, were investigated using a “closed” cranial window. We examined constrictor effects of norepinephrine on pial arterioles in the absence and presence of relatively selective α1,- (prazosin) and α2-(yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Yohimbine and prazosin inhibited pial arteriolar constriction induced by topical application of clonidine and phenylephrine (10−6 and 10−4 M, respectively), and yohimbine did not affect the response to topical phenylephrine. In one group diameter was 188 ± 13 (mean ± SEM) μm during control and 146 ± 12 (μm during 10−5 M norepinephrine (22 ± 5% constriction). Following yohimbine the same vessels did not constrict significantly. In another group 10−5 M norepinephrine constricted arterioles by 22 ± 5%, and this response was unaffected by prazosin (24 ± 5% constriction). We conclude that pial arterioles are responsive to both α1- and α2-adrenoceptor agonists, that intravenous administration of prazosin and yohimbine results in these drugs crossing the blood–brain barrier and inhibiting constrictor effects of agonists, and that norepinephrine constricts pial arterioles predominantly via α2-adrenoceptors.

Opioids and nitric oxide contribute to hypoxia-induced pial arterial vasodilation in newborn pigs

1995 ◽  
Vol 268 (1) ◽  
pp. H226-H232 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Direct Action ◽  
Opioid Antagonist ◽  
Opioid Agonist ◽  
Methionine Enkephalin ◽  
Mu Opioid ◽  
Cranial Window ◽  
Newborn Pigs ◽  
Synthase Inhibitor ◽  
Arteriolar Diameter

The present study was designed to investigate the contribution of opioids and nitric oxide (NO) to hypoxia-induced pial vasodilation. Newborn pigs equipped with a closed cranial window were used to measure pial arteriolar diameter and to collect cortical periarachnoid cerebrospinal fluid (CSF) for assay of opioids and guanosine 3',5'-cyclic monophosphate (cGMP). Hypoxia-induced pial dilation was potentiated by norbinaltorphimine, 10(-6) M, a kappa-opioid antagonist (25 +/- 2 vs. 33 +/- 3%, n = 5), but was blunted by beta-funaltrexamine, 10(-8) M, a mu-opioid antagonist (28 +/- 2 vs. 19 +/- 1%, n = 5). Hypoxia-induced vasodilation was associated with increased CSF methionine enkephalin, a mu-opioid agonist (884 +/- 29 vs. 2,638 +/- 387 pg/ml, n = 5). N omega-nitro-L-arginine (L-NNA), an NO synthase inhibitor (10(-6) M), also blunted hypoxia-induced vasodilation that was further diminished by coadministration of L-NNA and beta-funaltrexamine (26 +/- 2, 14 +/- 1, and 9 +/- 1%, respectively, n = 5). Reversal of the above order of antagonist administration resulted in similar inhibition of hypoxia-induced pial dilation. Hypoxia-induced vasodilation was also associated with an increase in CSF cGMP that was attenuated by L-NNA (2.1 +/- 0.1- vs. 1.1 +/- 0.2-fold change in CSF cGMP, n = 5). Sodium nitroprusside (10(-6) M) increased CSF cGMP and methionine enkephalin concentration similar to hypoxia. These data suggest that hypoxia-induced pial arterial vasodilation, in part, is due to NO and/or cGMP-induced methionine enkephalin release as well as the direct action of NO.

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