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.

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.

O2 radicals in arachidonate-induced increased blood-brain barrier permeability to proteins

1986 ◽  
Vol 251 (4) ◽  
pp. H693-H699 ◽  
Author(s):  
E. P. Wei ◽  
M. D. Ellison ◽  
H. A. Kontos ◽  
J. T. Povlishock
Keyword(s):  
Horseradish Peroxidase ◽  
Blood Brain Barrier ◽  
Topical Application ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Cranial Window ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Pial Arterioles

We studied the effect of topical application of arachidonate on the brain surface on blood-brain barrier permeability to either 125I-labeled human albumin or to horseradish peroxidase administered intravenously. Arachidonate was applied under a cranial window, and the concentration of albumin was measured in brain after elimination of the blood by perfusion-fixation. Permeability to 125I-labeled albumin was increased in the superficial 4 mm of the cortex but not in the deeper cortical layer 4-6 mm from the surface. This increased permeability to albumin was prevented by simultaneous topical application of superoxide dismutase (60 U/ml) and catalase (40 U/ml). Alterations in vascular permeability to horseradish peroxidase were evaluated in semiquantitative fashion, and they behaved similarly. Extravasated horseradish peroxidase was found in the wall of penetrating arterioles, and to a lesser extent in the wall of intraparenchymal vessels and capillaries, but not in the wall of pial arterioles or veins, although these latter vessels displayed focal endothelial lesions. We conclude that arachidonate increases the blood-brain barrier permeability to proteins. This increase in permeability is mediated by O2 radicals. The increased permeability occurs primarily in penetrating arterioles and not in pial arterioles or veins.

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)

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.

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.

Hemodilution causes size-dependent constriction of pial arterioles in the cat

1989 ◽  
Vol 257 (3) ◽  
pp. H912-H917 ◽  
Author(s):  
M. L. Hudak ◽  
M. D. Jones ◽  
A. S. Popel ◽  
R. C. Koehler ◽  
R. J. Traystman ◽  
...  
Keyword(s):  
Blood Gases ◽  
Base Line ◽  
Isovolemic Hemodilution ◽  
Size Dependent ◽  
Cranial Window ◽  
Arterial Blood ◽  
Equal Importance ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Cerebral Vasodilation

Cerebral blood flow (CBF) rises as hematocrit (Hct) falls. We previously attributed this rise in CBF to two independent factors of equal importance, decreased arterial O2 content and decreased blood viscosity. We hypothesized that decreased arterial O2 content would dilate cerebral arterioles and that the magnitude of the vasodilation would depend on the magnitude of the passive fall in vascular resistance attributable to decreased viscosity. The present study was designed to test the hypothesis that anemia is accompanied by cerebral vasodilation. Using a closed cranial window, we measured the diameters of 42 pial arterioles (35-305 microns) in 7 cats as serial isovolemic hemodilution lowered Hct by 44% from 31 +/- 4 to 17 +/- 3%. Hemodilution increased CBF (microsphere technique) but did not change mean arterial blood pressure or arterial blood gases. Anticipated vasodilation did not occur; instead, pial arterioles constricted as Hct fell. Maximum vasoconstriction was observed when Hct reached 65-70% of the initial value. Vasoconstriction lessened as Hct was lowered further, but arteriolar diameters at the lowest Hcts remained less than base-line levels. Constriction was greater in small (less than 100 microns) than in large (greater than or equal to 100 microns) arterioles. The initial constriction of pial arterioles may represent myogenic vasoconstriction in response to flow-induced vasodilation of more proximal portions of the cerebrovascular bed and/or to washout of an endogenous vasodilator. Arteriolar relaxation with more profound hemodilution may reflect superimposed metabolic vasodilation.

scholarly journals A Novel Algorithm for the Assessment of Blood-Brain Barrier Permeability Suggests That Brain Topical Application of Endothelin-1 Does Not Cause Early Opening of the Barrier in Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
D. Jorks ◽  
D. Milakara ◽  
M. Alam ◽  
E. J. Kang ◽  
S. Major ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Topical Application ◽  
Spatial Information ◽  
Ex Vivo ◽  
Brain Barrier ◽  
Special Equipment ◽  
Endothelin 1 ◽  
Cranial Window ◽  
Blood Brain ◽  
Bbb Opening

There are a number of different experimental methods for ex vivo assessment of blood-brain barrier (BBB) opening based on Evans blue dye extravasation. However, these methods require many different steps to prepare the brain and need special equipment for quantification. We here report a novel, simple, and fast semiquantitative algorithm to assess BBB integrity ex vivo. The method is particularly suitable for cranial window experiments, since it keeps the spatial information about where the BBB opened. We validated the algorithm using sham controls and the established model of brain topical application of the bile salt dehydrocholate for early BBB disruption. We then studied spreading depolarizations in the presence and the absence of the vasoconstrictor endothelin-1 and found no evidence of early BBB opening (three-hour time window). The algorithm can be used, for example, to assess BBB permeability ex vivo in combination with dynamic in vivo studies of BBB opening.

Endothelial and nonendothelial cyclooxygenase mediate rabbit pial arteriole dilation by bradykinin

1995 ◽  
Vol 268 (1) ◽  
pp. H458-H466 ◽  
Author(s):  
J. R. Copeland ◽  
K. A. Willoughby ◽  
T. M. Tynan ◽  
S. F. Moore ◽  
E. F. Ellis
Keyword(s):  
Selective Inhibition ◽  
Gas Mixture ◽  
Cerebral Microvessels ◽  
Co2 Gas ◽  
Cranial Window ◽  
Cyclooxygenase Activity ◽  
Window Technique ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
The Brain

Aspirin (acetylsalicylic acid, ASA) was administered to rabbits in an attempt to inhibit selectively endothelial cyclooxygenase activity and therefore to determine its role in bradykinin-induced radical-mediated dilation of cerebral arterioles. With the use of the cranial window technique in anesthetized rabbits, pial arteriolar diameters were recorded in response to topically applied bradykinin, acetylcholine, and ventilation with 10% O2-9% CO2 gas mixture. Prostaglandins were measured in isolated cerebral microvessels and cerebrospinal fluid (CSF) using radioimmunoassay. Microvessel prostaglandin production was reduced significantly by 90 mg/kg i.v. ASA, whereas acetylcholine-stimulated increases of CSF prostaglandins were not similarly affected. This treatment reduced bradykinin-induced dilation of pial arterioles by 47%. After concurrent 90 mg/kg i.v. ASA plus 300 microM ASA topically applied to the brain, stimulated increases of CSF prostaglandins were reduced by 79%, while bradykinin-induced dilation was reduced by 78%. ASA did not reduce the dilator activity of either acetylcholine or ventilation with 10% O2-9% CO2. Acetylcholine- but not bradykinin-induced dilation was reduced by NG-nitro-L-arginine methyl ester. These results indicate intravenous ASA produced a relatively selective inhibition of cerebral microvascular cyclooxygenase and partial inhibition of bradykinin-induced dilation. Further inhibition of dilation occurred following ASA administered both systemically and topically to the brain. This indicates two sources of cyclooxygenase, endothelial and nonendothelial, mediate the bradykinin-induced dilation of rabbit pial arterioles. Furthermore, systemic doses of ASA do not eliminate brain prostaglandin formation.

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.

Trigeminalectomy modifies pial arteriolar responses to hypertension or norepinephrine

1988 ◽  
Vol 255 (1) ◽  
pp. H1-H6 ◽  
Author(s):  
M. A. Moskowitz ◽  
E. P. Wei ◽  
K. Saito ◽  
H. A. Kontos
Keyword(s):  
Trigeminal Nerve ◽  
Severe Hypertension ◽  
Trigeminal Ganglia ◽  
Cerebral Vasculature ◽  
Arterial Pco2 ◽  
Cranial Window ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Two Sides

The responses of pial precapillary vessels were examined bilaterally using a closed cranial-window preparation in 11 anesthetized cats after chronic unilateral section of the trigeminal ganglia. During increases or decreases in arterial PCO2 or hypoxia, vasoconstrictor and vasodilator responses were symmetrical and appropriate on the two sides. The superfusion of vessels with norepinephrine (10 micrograms/ml) constricted large and small pial arterioles to a greater extent on the denervated side, and this difference persisted even after washing (P less than 0.02). After severe hypertension, small and large arterioles dilated on both sides, although to a greater extent on the innervated side. In 8 of 10 acutely hypertensive animals, extravasation of intravenously administered iodinated albumin was greater in the intact than deafferented hemisphere. These results suggest that the trigeminal nerve can modify the responses of cerebral arterioles and participate in the regulation of the cerebral vasculature.

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