scholarly journals Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD

2001 ◽  
Vol 281 (4) ◽  
pp. H1697-H1703 ◽  
Author(s):  
Sean P. Didion ◽  
Christopher A. Hathaway ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
Blood Vessels ◽  
Basilar Artery ◽  
Normal Activity ◽  
Cerebral Blood Vessels ◽  
Cranial Window ◽  
Copper Zinc ◽  
Cerebral Arterioles ◽  
And Function

The goal of this study was to examine the role of endogenous copper/zinc (CuZn)-superoxide dismutase (SOD) on superoxide levels and on responses of cerebral blood vessels to stimuli that are mediated by nitric oxide (acetylcholine) and cyclooxygenase-dependent mechanisms (bradykinin and arachidonic acid). Levels of superoxide in the rabbit basilar artery were measured using lucigenin-enhanced chemiluminescence (5 μM lucigenin). Diethyldithiocarbamate (DDC; 10 mM), an inhibitor of CuZn-SOD, increased superoxide levels by ∼2.4-fold ( P < 0.05) from a baseline value of 1.0 ± 0.2 relative light units · min−1 · mm−2(means ± SE). The diameter of cerebral arterioles (baseline diameter, 99 ± 3 μm) was also measured using a closed cranial window in anesthetized rabbits. Topical application of DDC attenuated responses to acetylcholine, bradykinin, and arachidonate, but not nitroprusside. For example, 10 μM arachidonic acid dilated cerebral arterioles by 40 ± 5 and 2 ± 2 μm under control conditions and after DDC, respectively ( P < 0.05). These inhibitory effects of DDC were reversed by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (10 mM). Arachidonate increased superoxide levels in the basilar artery moderately under normal conditions and this increase was greatly augmented in the presence of DDC. These findings suggest that endogenous CuZn-SOD limits superoxide levels under basal conditions and has a marked influence on increases in superoxide in vessels exposed to arachidonic acid. The results also suggest that nitric oxide- and cyclooxygenase-mediated responses in the cerebral microcirculation are dependent on normal activity of CuZn-SOD.

Response of cerebral blood vessels to an endogenous inhibitor of nitric oxide synthase

1995 ◽  
Vol 269 (5) ◽  
pp. H1522-H1527 ◽  
Author(s):  
F. M. Faraci ◽  
J. E. Brian ◽  
D. D. Heistad
Keyword(s):  
Nitric Oxide ◽  
Blood Vessels ◽  
No Synthase ◽  
Endogenous Inhibitor ◽  
Cerebral Blood Vessels ◽  
Endogenous Modulator ◽  
Cerebral Arterioles ◽  
High Concentrations ◽  
Baseline Diameter ◽  
Cerebral Vascular

We examined effects of NG,NG-dimethyl-L-arginine (asymmetric dimethylarginine, ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, on cerebral vascular responses using cranial windows in anesthetized rats and rabbits. Under control conditions in rats, topical application of 10 and 100 microM ADMA constricted the basilar artery by 9 +/- 2 and 19 +/- 1% (SE; P < 0.05, n = 8), respectively, from a baseline diameter of 213 +/- 19 microns. ADMA (10 and 100 microM) produced marked inhibition of vasodilation in response to acetylcholine without inhibiting vasodilatation in response to nitroprusside. ADMA (1-100 microM) inhibited activity of brain NO synthase (measured as the conversion of L-[14C]arginine to L-[14C]citrulline). In cerebrum and cerebellum, 50% inhibition of activity of NO synthase was produced by 2.3 +/- 0.4 and 1.8 +/- 0.1 microM ADMA, respectively. In rabbits, treatment with ADMA (300 microM) decreased baseline diameter of cerebral arterioles (control diameter = 93 +/- 10 microns) by 11 +/- 2% (P < 0.05, n = 10). In response to 1 microM acetylcholine, cerebral arterioles dilated by 36 +/- 6 and 13 +/- 4% (P < 0.05 vs. control) in the absence and presence of ADMA, respectively. Effects of ADMA were prevented by L-arginine. Thus ADMA inhibits activity of brain NO synthase and relaxation of cerebral blood vessels in response to acetylcholine. Because ADMA is produced in relatively high concentrations in brain, it may be an important endogenous modulator of cerebral vascular tone under resting conditions and in response to vasoactive stimuli.

scholarly journals Arachidonate dilates basilar artery by lipoxygenase-dependent mechanism and activation of K+channels

2001 ◽  
Vol 281 (1) ◽  
pp. R246-R253 ◽  
Author(s):  
Frank M. Faraci ◽  
Christopher G. Sobey ◽  
Sophocles Chrissobolis ◽  
Donald D. Lund ◽  
Donald D. Heistad ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Potassium Channels ◽  
Basilar Artery ◽  
Nordihydroguaiaretic Acid ◽  
Chiral Hplc ◽  
Lipoxygenase Pathway ◽  
Calcium Dependent ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
Baseline Diameter

Dilatation of cerebral arterioles in response to arachidonic acid is dependent on activity of cyclooxygenase. In this study, we examined mechanisms that mediate dilatation of the basilar artery in response to arachidonate. Diameter of the basilar artery (baseline diameter = 216 ± 7 μm) (means ± SE) was measured using a cranial window in anesthetized rats. Arachidonic acid (10 and 100 μM) produced concentration-dependent vasodilatation that was not inhibited by indomethacin (10 mg/kg iv) or N G-nitro-l-arginine (100 μM) but was inhibited markedly by baicalein (10 μM) or nordihydroguaiaretic acid (NDGA; 10 μM), inhibitors of the lipoxygenase pathway. Dilatation of the basilar artery was also inhibited markedly by tetraethylammonium ion (TEA; 1 mM) or iberiotoxin (50 nM), inhibitors of calcium-dependent potassium channels. For example, 10 μM arachidonate dilated the basilar artery by 19 ± 7 and 1 ± 1% in the absence and presence of iberiotoxin, respectively. Measurements of membrane potential indicated that arachidonate produced hyperpolarization of the basilar artery that was blocked completely by TEA. Incubation with [3H]arachidonic acid followed by reverse-phase and chiral HPLC indicated that the basilar artery produces relatively small quantities of prostanoids but large quantities of 12(S)-hydroxyeicosatetraenoic acid (12-S-HETE), a lipoxygenase product. Moreover, the production of 12-HETE was inhibited by baicalein or NDGA. These findings suggest that dilatation of the basilar artery in response to arachidonate is mediated by a product(s) of the lipoxygenase pathway, with activation of calcium-dependent potassium channels and hyperpolarization of vascular muscle.

scholarly journals Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Stem ◽  
Topical Application ◽  
Basilar Artery ◽  
Group Versus ◽  
Control Group ◽  
Cranial Window ◽  
Severe Hypotension ◽  
The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

scholarly journals Transient Focal Ischemia Increases Endothelial Nitric Oxide Synthase in Cerebral Blood Vessels

Stroke ◽  
2002 ◽  
Vol 33 (11) ◽  
pp. 2704-2710 ◽  
Author(s):  
Roland Veltkamp ◽  
Nishadi Rajapakse ◽  
Greg Robins ◽  
Michelle Puskar ◽  
Katsuyoshi Shimizu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Blood Vessels ◽  
Endothelial Nitric Oxide Synthase ◽  
Focal Ischemia ◽  
Cerebral Blood Vessels ◽  
Transient Focal Ischemia ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Expression and Function of Recombinant Endothelial Nitric Oxide Synthase Gene in Canine Basilar Artery

1997 ◽  
Vol 80 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Alex F.Y. Chen ◽  
Timothy O’Brien ◽  
Masato Tsutsui ◽  
Hiroyuki Kinoshita ◽  
Vincent J. Pompili ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Basilar Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Canine Basilar Artery ◽  
And Function ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Structure and Function of the Rat Basilar Artery During Chronic Nitric Oxide Synthase Inhibition

Stroke ◽  
1995 ◽  
Vol 26 (10) ◽  
pp. 1922-1929 ◽  
Author(s):  
Pierre Moreau ◽  
Hiroyuki Takase ◽  
Christoph F. Küng ◽  
Menno-M. van Rooijen ◽  
Thomas Schaffner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Basilar Artery ◽  
Structure And Function ◽  
And Function ◽  
Oxide Synthase

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.

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