scholarly journals Effect of Leukotrienes, 12-HETE, Histamine, Bradykinin, and 5-Hydroxytryptamine on in vivo Rabbit Cerebral Arteriolar Diameter

1985 ◽  
Vol 5 (4) ◽  
pp. 554-559 ◽  
Author(s):  
Toshiharu Kamitani ◽  
Marcia H. Little ◽  
Earl F. Ellis
Keyword(s):  
Pial Arteries ◽  
Peripheral Tissues ◽  
Cranial Window ◽  
Lipoxygenase Products ◽  
Cerebral Arterioles ◽  
Potent Vasoconstrictor ◽  
Arteriolar Vasodilation ◽  
Dose Dependent ◽  
Arteriolar Diameter

To determine the possible role that leukotrienes (LTs) may play in the regulation of cerebral blood flow, the responses of cerebral arterioles to LTs and 12-hydroxyeicosatetraenoic acid (12-HETE) were studied in vivo in rabbits equipped with a cranial window for direct observation of the microcirculation. Topical application of LTC, LTD4, or 12-HETE (1.6 × 10−9–3.1 × 10−6 M) neither constricted nor dilated the pial arteries. LTB4 produced only a 5% vasoconstriction at 3.0 × 10−6 M. However, bradykinin induced dose-dependent arteriolar vasodilation and histamine and 5-hydroxytryptamine induced dose-dependent arteriolar vasoconstriction. Although some LTs have potent vasoconstrictor activity in peripheral tissues and 5-lipoxygenase products have been hypothesized to be mediators of vasospasm after subarachnoid hemorrhage, LTB4, LTC4, LTD4, and 12-HETE apparently are unable to induce significant constriction of the cerebral arterioles in the anesthetized rabbit.

Mechanisms of endotoxin-induced dilatation of cerebral arterioles

1995 ◽  
Vol 269 (3) ◽  
pp. H783-H788 ◽  
Author(s):  
J. E. Brian ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
No Synthase ◽  
Vascular Responses ◽  
Time Points ◽  
Cranial Window ◽  
Inducible No Synthase ◽  
Calcitonin Gene ◽  
Cerebral Arterioles ◽  
Arteriolar Diameter ◽  
Inducible Nitric Oxide

Lipopolysaccharide (LPS; endotoxin) produces dilatation of cerebral arterioles in vivo which may be due, in part, to expression of inducible nitric oxide (NO) synthase. We tested the hypothesis that aminoguanidine, an inhibitor of inducible NO synthase, would reduce endotoxin-induced dilatation of cerebral arterioles. Because mechanisms other than expression of inducible NO synthase may contribute to endotoxin-induced dilatation of cerebral arterioles, we also tested the hypothesis that calcitonin gene-related peptide (CGRP) contributes to vascular responses to endotoxin. Cerebral arteriolar diameter was measured using a closed cranial window in anesthetized rabbits under control conditions [77 +/- 3 (SE) microns] and during topical application of endotoxin (100 micrograms/ml). After 4 h, diameter of cerebral arterioles increased by 41 +/- 5%. Coapplication of aminoguanidine (0.3 mM) with endotoxin reduced vasodilatation at all time points (30 min to 4 h). Relative to control values, endotoxin treatment increased guanosine 3',5'-cyclic monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) by approximately 20 fold at 4 h. Aminoguanidine attenuated the endotoxin-induced increased in CSF cGMP concentration. Aminoguanidine (0.3 mM) did not alter acetylcholine-mediated dilatation of cerebral arterioles. Coapplication of CGRP-(8-37) (0.5 microM), a specific blocker of CGRP receptors, with endotoxin significantly reduced vasodilatation in response to endotoxin at 2, 3, and 4 h. Thus 1) aminoguanidine inhibits endotoxin- but not acetylcholine-mediated dilatation of cerebral arterioles, and 2) activation of CGRP receptors mediates a portion of endotoxin-induced dilation of cerebral arterioles.

Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles

1990 ◽  
Vol 258 (6) ◽  
pp. H1840-H1846 ◽  
Author(s):  
R. L. Haberl ◽  
F. Anneser ◽  
A. Villringer ◽  
K. M. Einhaupl
Keyword(s):  
Methylene Blue ◽  
Angiotensin Ii ◽  
Light Illumination ◽  
Ang Ii ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
Fluorescein Dye ◽  
Arteriolar Vasodilation ◽  
Dose Dependent ◽  
Dependent Mechanism

We evaluated the response of cerebral arterioles to angiotensin II (ANG II) in anesthetized rats equipped with a closed cranial window. Topical application of 10(-10)-10(-5) M ANG II induced dose-dependent arteriolar vasodilation. Maximum vasodilation of 24 +/- 2.2% (+/- SE) was attained at a concentration of 10(-6) M ANG II. The dilation in response to ANG II was blocked by 3 micrograms/ml indomethacin, a cyclooxygenase inhibitor, and was reversed to minimal vasoconstriction by 10(-5) M methylene blue, a substance that has been reported to eliminate endothelium-dependent vasodilation. Coapplication of indomethacin with methylene blue reduced the arteriolar response to ANG II to a similar extent as the application of indomethacin alone. Indomethacin or methylene blue did not inhibit the vasodilation induced by 10(-5) M adenosine, which is not endothelium and cyclooxygenase dependent. Mercury light illumination of the pial vessels after intravenous injection of fluorescein dye, a technique that has been used by others to functionally damage endothelial cells, reversed ANG II (10(-6) M)-induced vasodilation into a -14.2 +/- 2.3% constriction while not affecting the response to adenosine. Our data suggest that ANG II produces vasodilator responses of rat cerebral arterioles by the release of a factor that is derived from the endothelium and may be generated through a cyclooxygenase-dependent mechanism.

Dilation of cerebral arterioles by cytochrome P-450 metabolites of arachidonic acid

1990 ◽  
Vol 259 (4) ◽  
pp. H1171-H1177 ◽  
Author(s):  
E. F. Ellis ◽  
R. J. Police ◽  
L. Yancey ◽  
J. S. McKinney ◽  
S. C. Amruthesh
Keyword(s):  
Arachidonic Acid ◽  
Oxygen Radicals ◽  
Cyclooxygenase Inhibitors ◽  
Epoxyeicosatrienoic Acid ◽  
Cranial Window ◽  
Window Technique ◽  
Cerebral Arterioles ◽  
Pg E2 ◽  
Cytochrome P 450

We have recently shown that brain tissue can synthesize cytochrome P-450 monooxygenase metabolites of arachidonic acid (AA), including 5,6-epoxyeicosatrienoic acid (5,6-EET), and 14,15-EET. The purpose of this investigation was to determine the vasoactivity of EETs and AA on the cerebral microcirculation. Pial arteriolar diameter was measured in rabbits and cats using in vivo microscopy and the closed cranial window technique. Prostaglandin (PG) E2 and 6-keto-PGF1 alpha formed by the brain cortex during application of these fatty acids was measured in cerebrospinal fluid by use of radioimmunoassay. A transient dose-dependent dilation was produced by 5,6-EET (1-15 micrograms/ml), with the maximum being 23% of control in both species. Other EETs had little or no activity, and AA-induced dilation was greater in rabbits than in cats. Indomethacin or superoxide dismutase plus catalase prevented dilation by 5,6-EET and AA, indicating that both produce dilation via cyclooxygenase-dependent oxygen radicals. PGE2 and 6-keto-PGF1 alpha levels were increased by AA but not by EETs, implying that EETs do not directly activate AA metabolism. Since 5,6-EET, but not other EETs, is known to be a substrate for cyclooxygenase, our data are consistent with brain cyclooxygenase metabolism of 5,6-EET with concomitant generation of dilator oxygen radicals. An implication of these results is that many previous studies of the cerebral circulation which based conclusions on results with cyclooxygenase inhibitors may need to be additionally interpreted.

Localization of TRPA1 channels and characterization of TRPA1 mediated responses in dural and pial arteries in vivo after intracarotid infusion of Na2S

Cephalalgia ◽  
2020 ◽  
Vol 40 (12) ◽  
pp. 1310-1320
Author(s):  
Anna Koldbro Hansted ◽  
Lars Jørn Jensen ◽  
Jes Olesen ◽  
Inger Jansen-Olesen
Keyword(s):  
Dura Mater ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Pial Arteries ◽  
Cranial Window ◽  
Cgrp Receptor Antagonist ◽  
Transient Receptor ◽  
Channel Dependent

Background The Transient Receptor Potential Ankyrin 1 (TRPA1) channel might play a role in migraine. However, different mechanisms for this have been suggested. The purpose of our study was to investigate the localization and significance of TRPA1 channels in rat pial and dural arteries. Methods Immunofluorescence microscopy was used to localize TRPA1 channels in dural arteries, pial arteries, dura mater and trigeminal ganglion. The genuine closed cranial window model was used to examine the effect of Na2S, a donor of the TRPA1 channel opener H2S, on the diameter of pial and dural arteries. Further, we performed blocking experiments with TRPA1 antagonist HC-030031, calcitonin gene-related peptide (CGRP) receptor antagonist olcegepant and KCa3.1 channel blocker TRAM-34. Results TRPA1 channels were localized to the endothelium of both dural and pial arteries and in nerve fibers in dura mater. Further, we found TRPA1 expression in the membrane of trigeminal ganglia neuronal cells, some of them also staining for CGRP. Na2S caused dilation of both dural and pial arteries. In dural arteries, this was inhibited by HC-030031 and olcegepant. In pial arteries, the dilation was inhibited by TRAM-34, suggesting involvement of the KCa3.1 channel. Conclusion Na2S causes a TRPA1- and CGRP-dependent dilation of dural arteries and a KCa3.1 channel-dependent dilation of pial arteries in rats.

Indomethacin-sensitive CO2 reactivity of cerebral arterioles is restored by vasodilator prostaglandin

1994 ◽  
Vol 266 (4) ◽  
pp. H1332-H1338 ◽  
Author(s):  
L. C. Wagerle ◽  
P. A. Degiulio
Keyword(s):  
Sodium Nitroprusside ◽  
Intracellular Signaling ◽  
Receptor Activation ◽  
Cyclooxygenase Inhibitors ◽  
Relaxation Response ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Vasodilator Response ◽  
Cerebral Arterioles ◽  
Arteriolar Diameter

To investigate the role of vasodilator prostanoids in the CO2-induced relaxation of cerebral arterioles, the present study examined the effect of exogenous prostaglandin (PG) E2 and nonprostanoid vasodilators, adenosine and sodium nitroprusside, on the indomethacin-impaired pial arteriolar response to CO2 in newborn piglets. Reactivity of pial arterioles (52-131 microns diam) was determined using a closed cranial window with intravital microscopy. Cortical prostanoid synthesis was assessed by analyzing for select prostanoids in cerebrospinal fluid sampled from under the cranial window. Inhalation of 7% CO2 caused an elevation of cortical 6-keto-PGF1 alpha and thromboxane (Tx) B2 and increased pial arteriolar diameter by 34 +/- 5%. Two cyclooxygenase inhibitors, indomethacin (5 mg/kg i.v.) and ibuprofen (30 mg/kg i.v.), abolished the CO2-induced elevation of cortical prostanoids. Indomethacin, but not ibuprofen, blocked the CO2-induced increase in pial arteriolar diameter. The indomethacin-impaired vasodilator response to CO2 was restored when PGE2 (0.1-1 microM) was applied topically to the cortical surface. Adenosine (1-100 microM) and sodium nitroprusside (0.5 microM) only partially restored the vasodilator response to CO2. The data suggest that vasodilator prostanoids facilitate cerebrovascular relaxation to CO2 and may play a permissive role in the relaxation response of vascular smooth muscle. The fact that adenosine (adenosine 3',5'-cyclic monophosphate-mediated dilator) and sodium nitroprusside (guanosine 3',5'-cyclic monophosphate-mediated dilator), were partially effective suggests a role for those intracellular signaling pathways. We speculate that receptor activation of intracellular pathways may alter Ca2+ sensitivity of the contractile apparatus in such a way that the relaxation response to CO2 can occur.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glutamine-dependent inhibition of pial arteriolar dilation to acetylcholine with and without hyperammonemia in the rat

2005 ◽  
Vol 288 (6) ◽  
pp. R1612-R1619 ◽  
Author(s):  
Tetsu Kawaguchi ◽  
Saul W. Brusilow ◽  
Richard J. Traystman ◽  
Raymond C. Koehler
Keyword(s):  
Intravenous Infusion ◽  
Ammonium Acetate ◽  
Ammonia Concentration ◽  
Inhibitory Effect ◽  
Glutamine Concentration ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
Cerebral Glutamine

Glutamine has been shown to influence endothelial-dependent relaxation and nitric oxide production in vitro, possibly by limiting arginine availability, but its effects in vivo have not been well studied. Hyperammonemia is a pathophysiological condition in which glutamine is elevated and contributes to depressed CO2 reactivity of cerebral arterioles. We tested the hypothesis that acute hyperammonemia decreases pial arteriolar dilation to acetylcholine in vivo and that this decrease could be prevented by inhibiting glutamine synthetase with l-methionine- S-sulfoximine (MSO) or by intravenous infusion of l-arginine. Pial arteriolar diameter responses to topical superfusion of acetylcholine were measured in anesthetized rats before and at 6 h of infusion of either sodium or ammonium acetate. Ammonium acetate infusion increased plasma ammonia concentration from ∼30 to ∼600 μM and increased cerebral glutamine concentration fourfold. Arteriolar dilation to acetylcholine was intact after infusion of sodium acetate in groups pretreated with vehicle or with MSO plus methionine, which was coadministered to prevent MSO-induced seizures. In contrast, dilation in response to acetylcholine was completely blocked in hyperammonemic groups pretreated with vehicle or methionine alone. However, MSO plus methionine administration before hyperammonemia, which maintained cerebral glutamine concentration at control values, preserved acetylcholine dilation. Intravenous infusion of l-arginine during the last 2 h of the ammonium acetate infusion partially restored dilation to acetylcholine without reducing cerebral glutamine accumulation. Superfusion of 1 or 2 mM l-glutamine through the cranial window for 1 h in the absence of hyperammonemia attenuated acetylcholine dilation but had no effect on endothelial-independent dilation to nitroprusside. We conclude that 1) hyperammonemia reduces acetylcholine-evoked dilation in cerebral arterioles, 2) this reduction depends on increased glutamine rather than ammonium ions, and 3) increasing arginine partially overcomes the inhibitory effect of glutamine.

scholarly journals Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide: A Vasoactive Role in the Cerebral Circulation

2005 ◽  
Vol 25 (10) ◽  
pp. 1376-1385 ◽  
Author(s):  
Jeffrey J Iliff ◽  
Nabil J Alkayed ◽  
Kiarash J Gloshani ◽  
Richard J Traystman ◽  
G Alexander West
Keyword(s):  
Cerebral Circulation ◽  
Vascular Response ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Injury Model ◽  
Cart Peptide ◽  
Cerebral Arterioles ◽  
Specific Antagonist ◽  
Potent Vasoconstrictor ◽  
Dose Dependent

Cocaine- and amphetamine-regulated transcript (CART) peptides are known to be involved in the stress response and have been implicated in the regulation of the cardiovascular system. We evaluated the direct vasoactive properties of CART in the cerebral circulation and its potential mechanisms of action. Penetrating cerebral arterioles, isolated from male Sprague—Dawley rats, were cannulated using a concentric micropipette setup, pressurized and perfused. The vascular response to intraluminal and extraluminal CART peptide was characterized. The endothelium dependence of this response was assessed by means of the endothelial light—dye injury model. The nonspecific endothelin receptor antagonist PD-145065, the ETA-specific antagonist BQ-123, the ETB-specific antagonist BQ-788, and the inhibitor of endothelin-converting enzyme phosphoramidon were used to characterize the involvement of the endothelin pathway in the vascular response to CART peptide. Extraluminal and intraluminal application of CART peptide (0.1 nm to 1 μmol/L) evoked a long-lasting dose-dependent constriction of isolated penetrating cerebral arterioles to ~80% of resting myogenic tone. Disruption of the endothelium by the endothelial light/dye injury model resulted in the abolition of this response ( P<0.05). Extraluminal administration of PD-145065, BQ-123, and phosphoramidon blocked the constriction response to CART peptide ( P<0.01). The ETB antagonist, BQ-788, did not alter the constriction response to CART peptide. Cocaine- and amphetamine-regulated transcript peptide is a potent vasoconstrictor in the cerebral circulation. Its direct vasoactive properties are endothelium-dependent and are mediated by ETA, not ETB, endothelin receptors.

Direct Effects of α1-and α2-AdrenergicAgonists on Spinal and Cerebral Pial Vessels in Dogs 

1999 ◽  
Vol 91 (2) ◽  
pp. 479-485 ◽  
Author(s):  
Hiroki Iida ◽  
Hiroto Ohata ◽  
Mami Iida ◽  
Yukinaga Watanabe ◽  
Shuji Dohi
Keyword(s):  
Topical Administration ◽  
Vessel Diameter ◽  
Dependent Manner ◽  
Adrenergic Agonists ◽  
Concentration Dependent Manner ◽  
Cranial Window ◽  
Pial Vessels ◽  
Cerebral Arterioles ◽  
Pial Vessel

Background The effects of adrenergic agonists, often used as local anesthetic additives or spinal analgesics, on spinal vessels have not been firmly established. The authors investigated the effects of alpha2- and alpha1-adrenergic agonists on spinal and cerebral pial vessels in vivo. Methods Pentobarbital-anesthetized dogs (n = 28) were prepared for measurement of spinal pial-vessel diameter in a spinal-window preparation. The authors applied dexmedetomidine, clonidine, phenylephrine, or epinephrine in three different concentrations (0.5, 5.0, and 50 microg/ml; [2.1, 1.9, 2.5, and 2.3] x [10(-6), 10(-5), and 10(-4)] M, respectively) under the window (one drug in each dog) and measured spinal pial arteriolar and venular diameters in a sequential manner. To enable the comparison of their effects on cerebral vessels, the authors also administered these drugs under a cranial window. Results On topical administration, each drug constricted spinal pial arterioles in a concentration-dependent manner. Phenylephrine and epinephrine induced a significantly larger arteriolar constriction than dexmedetomidine or clonidine at 5 microg/ml (8%, 11%, 0%, and 1%, respectively). Spinal pial venules tended to be less constricted than arterioles. In cerebral arterioles, greater constrictions were induced by dexmedetomidine and clonidine than those induced by phenylephrine and epinephrine (14%, 8%, 0%, and 1%, respectively). Cerebral pial venules tended to exhibit larger constrictions than cerebral arterioles (unlike in spinal vessels). Conclusion Dexmedetomidine and clonidine constricted spinal vessels in a concentration-dependent manner, but such vasoconstrictions were smaller than those induced by phenylephrine and epinephrine.

Regulation of arteriolar tone and responses via L-arginine pathway in skeletal muscle

1992 ◽  
Vol 262 (4) ◽  
pp. H987-H992 ◽  
Author(s):  
G. Kaley ◽  
A. Koller ◽  
J. M. Rodenburg ◽  
E. J. Messina ◽  
M. S. Wolin
Keyword(s):  
Skeletal Muscle ◽  
Vascular Tone ◽  
Topical Administration ◽  
Systemic Blood Pressure ◽  
Vasoactive Agents ◽  
Skeletal Muscle Microcirculation ◽  
Arteriolar Tone ◽  
Dose Dependent ◽  
Arteriolar Diameter

With in vivo television microscopy, changes in arteriolar diameter to topical administration of various vasoactive agents were examined in the absence or in the presence of NG-monomethyl-L-arginine (L-NMMA, topical 100 microM) or NG-nitro-L-arginine (L-NNA, 2.5 microM, 20 microliters/min ia), specific inhibitors of endothelium-derived relaxing factor (EDRF) biosynthesis. In cremaster muscle arterioles (15-22 microns) of rats (n = 6-11), dilations to acetylcholine (1-100 ng) were significantly inhibited (60-70%) by either of the arginine analogues. This inhibition was reversed by subsequent administration of 1 mM L-arginine. Dose-dependent constriction to norepinephrine was enhanced by L-NMMA. Indomethacin treatment reduced arteriolar dilation to bradykinin (BK, 1-100 ng), which was significantly inhibited by additional administration of L-NNA. Application of L-NNA first, followed by additional indomethacin, elicited similar results. Dilations to sodium nitroprusside and adenosine were not reduced in the presence of the inhibitors. L-NMMA or L-NNA caused no change in systemic blood pressure but elicited a significant reduction in arteriolar diameter; this effect was not reversed by 1 mM L-arginine. These data demonstrate the presence of an L-arginine pathway to produce EDRF (nitric oxide) in skeletal muscle microcirculation that mediates and/or modulates arteriolar responses to vasoactive agents and could contribute to the regulation of basal vascular tone.

Potassium channels modulate cerebral autoregulation during acute hypertension

2000 ◽  
Vol 278 (6) ◽  
pp. H2003-H2007 ◽  
Author(s):  
Roberto Paternò ◽  
Donald D. Heistad ◽  
Frank M. Faraci ◽  
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Cerebral Autoregulation ◽  
Acute Hypertension ◽  
Calcium Dependent ◽  
Control Value ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
Arteriolar Diameter ◽  
Baseline Diameter

We tested the hypothesis that constriction of cerebral arterioles during acute increases in blood pressure is attenuated by activation of potassium (K+) channels. We tested the effects of inhibitors of calcium-dependent K+ channels [iberiotoxin (50 nM) and tetraethylammonium (TEA, 1 mM)] on changes in arteriolar diameter during acute hypertension. Diameter of cerebral arterioles (baseline diameter = 46 ± 2 μm, mean ± SE) was measured using a cranial window in anesthetized rats. Arterial pressure was increased from a control value of 96 ± 1 mmHg to 130, 150, 170, and 200 mmHg by intravenous infusion of phenylephrine. Increases in arterial pressure from baseline to 130 and 150 mmHg decreased the diameter of cerebral arterioles by 5–10%. Greater increases in arterial pressure produced large increases in arteriolar diameter (i.e., “breakthrough of autoregulation”). Iberiotoxin or TEA inhibited increases in arteriolar diameter when arterial pressure was increased to 170 and 200 mmHg. The change in arteriolar diameter at 200 mmHg was 20 ± 3% and −1 ± 4% in the absence and presence of iberiotoxin, respectively. These findings suggest that calcium-dependent K+ channels attenuate cerebral microvascular constriction during acute increases in arterial pressure, and that increases in arteriolar diameter at high levels of arterial pressure are not simply a passive phenomenon.

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