scholarly journals Effects of NADH and NADPH on superoxide levels and cerebral vascular tone

2002 ◽  
Vol 282 (2) ◽  
pp. H688-H695 ◽  
Author(s):  
Sean P. Didion ◽  
Frank M. Faraci
Keyword(s):  
Basilar Artery ◽  
Vascular Tone ◽  
Disulfonic Acid ◽  
Cranial Window ◽  
Diphenylene Iodonium ◽  
Basilar Arteries ◽  
Cerebral Arterioles ◽  
Cerebral Vascular

Reactive oxygen species are important modulators of cerebral vascular tone. Recent evidence, mainly from the aorta, suggests that NAD(P)H oxidase is a major source of vascular superoxide. The goal of the present study was to examine the effects of NADH and NADPH that are commonly used to stimulate NAD(P)H oxidase activity, on superoxide levels and cerebral vascular tone. Basilar arteries and cerebral arterioles from normal rabbits were studied in vitro using isolated tissue baths and in vivo using a cranial window, respectively. In the basilar artery, NADH produced a biphasic response; low concentrations (0.1–10 μM NADH) produced marked relaxation, whereas higher concentrations (30–100 μM NADH) produced contraction. Responses to NADH were significantly ( P < 0.05) inhibited in the presence of 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron; a scavenger of superoxide, 10 mM). In contrast, NADPH (10–100 μM) produced moderate contraction of the basilar artery, which was inhibited in the presence of Tiron. In vivo, NADH produced Tiron-sensitive dilatation of cerebral arterioles. NADH and NADPH dose dependently increased superoxide levels in the basilar artery, as detected by lucigenin (5 μM)-enhanced chemiluminescence, but increases in superoxide were significantly greater for NADPH than NADH. These increases in superoxide were markedly reduced in the presence of polyethylene glycol-superoxide dismutase (300 U/ml) or diphenylene iodonium [0.1 mM, an inhibitor of flavin-containing enzymes, including NAD(P)H oxidase] but were not affected by indomethacin, N G-nitro-l-arginine, or allopurinol. These data suggest that NADH- and NADPH-induced changes in cerebral vascular tone are mediated by superoxide, produced by a flavin-containing enzyme, most likely NAD(P)H oxidase, but not xanthine oxidase or nitric oxide synthase.

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.

Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery

1992 ◽  
Vol 263 (6) ◽  
pp. H1643-H1649 ◽  
Author(s):  
M. A. Murray ◽  
F. M. Faraci ◽  
D. D. Heistad
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Basilar Artery ◽  
Arginine Vasopressin ◽  
Vessel Diameter ◽  
Pkc Inhibitor ◽  
Cranial Window ◽  
Kinase C ◽  
Basilar Arteries

The goal of this study was to determine whether inhibitors of protein kinase C (PKC) attenuate constrictor responses of the basilar artery in vivo to endothelin and arginine vasopressin. In anesthetized rats, the diameter of basilar arteries was measured through a cranial window [control diameter 218 +/- 3 (SE) microns]. Vessel diameter was measured during topical application of agonists and antagonists. Sphingosine (10(-6) M), a PKC inhibitor that binds to the regulatory site of PKC, attenuated vasoconstriction in response to endothelin (10(-9), 10(-8), and 10(-7) M) and vasopressin (10(-9) and 10(-8) M). H-7 (10(-9) M), a PKC inhibitor that binds to the catalytic site of PKC, also inhibited vasoconstriction in response to endothelin and vasopressin. Sphingosine and H-7 did not affect baseline diameter and did not attenuate vasoconstriction in response to prostaglandin (PG) F2 alpha. The V1 antagonist [d(CH2)5Tyr(Me)]arginine vasopressin (10(-8) M) significantly inhibited constriction in response to vasopressin (10(-9) and 10(-8) M) but not PGF2 alpha (10(-6) M). These observations suggest that activation of PKC may contribute to endothelin-induced constriction of the basilar artery in vivo and that PKC may also be a mediator of V1-receptor-mediated constriction of the basilar artery in response to vasopressin.

scholarly journals Role of Hydrogen Peroxide and the Impact of Glutathione Peroxidase-1 in Regulation of Cerebral Vascular Tone

2009 ◽  
Vol 29 (6) ◽  
pp. 1130-1137 ◽  
Author(s):  
Mary L Modrick ◽  
Sean P Didion ◽  
Cynthia M Lynch ◽  
Sanjana Dayal ◽  
Steven R Lentz ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Glutathione Peroxidase ◽  
Vascular Effects ◽  
Vascular Responses ◽  
Basilar Arteries ◽  
The Impact ◽  
Cerebral Vascular

Although arachidonic acid (AA) has diverse vascular effects, the mechanisms that mediate these effects are incompletely defined. The goal of our study was to use genetic approaches to examine the role of hydrogen peroxide (H2O2), glutathione peroxidase (Gpx1, which degrades H2O2), and CuZn-superoxide dismutase (SOD1, which produces H2O2 from superoxide) in mediating and in determining vascular responses to AA. In basilar arteries in vitro, AA produced dilation in nontransgenic mice, and this response was reduced markedly in transgenic mice overexpressing Gpx1 (Gpx1 Tg) or in those genetically deficient in SOD1. For example, AA (1 nmol/L to 1 μmol/L) dilated the basilar artery and this response was reduced by ∼90% in Gpx1 Tg mice ( P<0.01), although responses to acetylcholine were not altered. Dilation of cerebral arterioles in vivo in response to AA was inhibited by ∼50% by treatment with catalase (300 U/mL) ( P<0.05) and reduced by as much as 90% in Gpx1 Tg mice compared with that in controls ( P<0.05). These results provide the first evidence that Gpx1 has functional effects in the cerebral circulation, and that AA-induced vascular effects are mediated by H2O2 produced by SOD1. In contrast, cerebral vascular responses to the endothelium-dependent agonist acetylcholine are not mediated by H2O2.

scholarly journals Application of the 1-µsec pulsed-dye laser to the treatment of experimental cerebral vasospasm

1991 ◽  
Vol 75 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Atsushi Teramura ◽  
Robert Macfarlane ◽  
Christopher J. Owen ◽  
Ralph de la Torre ◽  
Kenton W. Gregory ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Laser Energy ◽  
Autologous Blood ◽  
Preliminary Investigation ◽  
Dye Laser ◽  
Pulsed Dye Laser ◽  
Content Type

✓ Laser energy of 480 nm was applied in 1-µsec pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-µm fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood, 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-µsec pulsed-dye laser may be of benefit in the treatment of cerebral vasospasm.

P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function

2002 ◽  
Vol 82 (1) ◽  
pp. 131-185 ◽  
Author(s):  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Vascular Tone ◽  
Mesangial Cells ◽  
Cardiovascular Function ◽  
Tubuloglomerular Feedback ◽  
Peripheral Vasculature ◽  
Therapeutic Benefits

Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K+channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca2+-activated K+channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue Po2both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na+transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits.

Vasomotion of basilar arteries in vivo

1990 ◽  
Vol 258 (6) ◽  
pp. H1829-H1834 ◽  
Author(s):  
K. Fujii ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
Moderate Hypertension ◽  
Vessel Diameter ◽  
Base Line ◽  
Large Artery ◽  
Cranial Window ◽  
Basilar Arteries ◽  
The Mean ◽  
Rhythmic Change ◽  
The Brain

Vasomotion is a rhythmic change in vascular caliber that has been described in vivo mainly in peripheral arterioles. In this study, we have characterized vasomotion in a large artery of the brain in vivo. In anesthetized rats, spontaneous vasomotion was observed in 38 of 47 basilar arteries visualized through a cranial window. Base-line arterial diameter was 259 +/- 9 (means +/- SE) microns. Under control conditions, the frequency of vasomotion was 4.8 +/- 0.2 cycles/min, and the amplitude was 19 +/- 2% of the mean diameter. Vasomotion usually occurred simultaneously along the entire length of the vessel, but in some arteries it propagated in either direction. Moderate hypertension (phenylephrine) or vasoconstriction induced by topical application of serotonin, vasopressin, or the thromboxane analogue U 46619 increased the frequency of vasomotion. Moderate hypotension or vasodilation induced by nitroglycerin, adenosine, or acetylcholine decreased the frequency. Marked hypertension, hypotension, or vasodilatation abolished vasomotion. Thus vasomotion of the basilar artery in vivo 1) is common and of relatively large amplitude, 2) does not seem to be driven by a single pacemaker, and 3) is dependent on vessel diameter or vasomotor tone.

In Vivo Retrieval of a Trapped Merci Embolectomy Device: Technical Case Report

2010 ◽  
Vol 67 (3) ◽  
pp. onsE304-onsE304 ◽  
Author(s):  
Ajeet Gordhan ◽  
John Soliman
Keyword(s):  
Vertebral Artery ◽  
Conformational Changes ◽  
Basilar Artery ◽  
Technical Note ◽  
Vessel Injury ◽  
Artery Segment ◽  
In Vitro Assessment ◽  
Artery Flow

Abstract BACKGROUND AND IMPORTANCE: This technical note describes a complication related to the use of the Merci embolectomy device not previously reported. The device can induce critical flow limitation within an accessed vessel because of a combination of vasospasm and anatomic conformational changes. Furthermore, this can limit the safe removal of the device from intracranial vasculature. We present a novel rescue technique that can be used to safely retrieve the entrapped Merci device without inciting localized vessel injury. CLINICAL PRESENTATION: A 51-year-old male with embolic occlusion of the distal basilar artery and dissection-related occlusion of the left cervical vertebral underwent mechanical thrombolysis. Flow-limiting vasospasm and/or anatomic conformational changes/ telescoping of the intracranial right vertebral artery segment was induced during deployment with subsequent entrapment of the device. Reclamation of the entrapped device was performed by initially removing the Merci microcatheter. The entrapped and fixated device was then resheathed into a 4F slip catheter within the intracranial vertebral artery. The Merci device and the slip catheter were then removed. Right vertebral and proximal basilar artery flow was reestablished after removal of the Merci device. Successful clot extraction was thereafter performed using a microsnare. CONCLUSION: In vitro assessment of the device has demonstrated its propensity to induce vasospasm. In vivo entrapment of the device has not been previously reported. Successful retrieval can be achieved if the Merci device becomes entrapped and fixated. This may be an important consideration as increased utilization of the device occurs.

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.

Influence of SIN-1 on Platelet Ca2+ Handling in Patients with Suspected Coronary Artery Disease: Ex Vivo and In Vitro Studies

2000 ◽  
Vol 83 (05) ◽  
pp. 752-758 ◽  
Author(s):  
Claude Le Feuvre ◽  
Annie Brunet ◽  
Thuc Do Pham ◽  
Jean-Philippe Metzger ◽  
André Vacheron ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Vascular Tone ◽  
Ex Vivo ◽  
Suspected Coronary Artery Disease ◽  
In Vitro Studies ◽  
H2o2 Formation ◽  
Artery Disease ◽  
Dose Dependent

SummaryThe 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2−). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation.This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2− from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2− scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect.This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2− release, independently of H2O2 formation.

scholarly journals The Functional and Structural Changes in the Basilar Artery Due to Overpressure Blast Injury

2015 ◽  
Vol 35 (12) ◽  
pp. 1950-1956 ◽  
Author(s):  
Hale Z Toklu ◽  
Judy Muller-Delp ◽  
Zhihui Yang ◽  
Şehkar Oktay ◽  
Yasemin Sakarya ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Vascular Function ◽  
Structural Changes ◽  
Sprague Dawley ◽  
Endothelin 1 ◽  
Msec Duration ◽  
Basilar Arteries ◽  
Wave Induced ◽  
Endothelial Nitric Oxide ◽  
Cerebral Vascular

Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10−12 to 10−7 mol/L), acetylcholine (ACh) (10−10 to 10−4 mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10−10 to 10−4 mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ETA) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI.

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