Critical Role of Endothelial Nitric Oxide Synthase and Cyclooxygenase in Response of Rabbit Basilar Artery to Serotonin

Sercombe, Richard; Sercombe, Christine; Oudart, Nicole; Seylaz, Jacques

doi:10.1254/jjp.90.67

Cited by 10 publications

(7 citation statements)

References 47 publications

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“…In the rabbit basilar artery, endothelium-dependent relaxation to acetylcholine is primarily mediated by nitric oxide. Cyclooxygenase blockade by indomethacin has minimal effect on vasodilatation induced by acetylcholine 18,19. Our results with AdGFP-transduced control basilar arteries are in agreement with these reports as indomethacin did not significantly inhibit the maximal relaxations to acetylcholine.…”

Section: Discussionsupporting

confidence: 92%

Brain-Derived Neurotrophic Factor Stimulates Production of Prostacyclin in Cerebral Arteries

Santhanam

Smith

Katušić

2010

Stroke

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Background and Purpose-The role of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B, in control of cerebral circulation is poorly understood. The present study was designed to investigate the cerebral vascular effects of BDNF in vivo. Methods-Replication incompetent adenovirus encoding either rat BDNF (AdBDNF) or green fluorescent protein was injected intracisternally into rabbits. Forty-eight hours later, animals were euthanized. Plasma and cerebrospinal fluid levels of BDNF were measured by enzyme-linked immunosorbent assay, vasomotor function of isolated basilar arteries was studied in organ chambers, protein expression in the basilar arteries was studied by Western blotting, prostanoid levels were measured by enzyme-linked immunosorbent assay, and cyclic adenosine 3Ј,5Ј-monophosphate levels were measured by radioimmunoassay. Results-The levels of BDNF in the cerebrospinal fluid were significantly elevated in AdBDNF-treated rabbits as compared with adenovirus encoding green fluorescent protein-treated rabbits (37Ϯ5 ng/mL versus 0.006Ϯ0.003 ng/mL, respectively; PϽ0.05; nϭ14). Western blotting studies revealed that in basilar arteries, AdBDNF increased protein expression of prostacyclin synthase, whereas expression of endothelial nitric oxide synthase and phosphorylated (Ser 1177) endothelial nitric oxide synthase remained unchanged. During incubation with arachidonic acid (1 mol/L), PGI 2 production and levels of cyclic adenosine 3Ј,5Ј-monophosphate were significantly elevated only in AdBDNF-treated rabbit basilar arteries (PϽ0.05, nϭ6). Relaxations to acetylcholine (10 Ϫ9 to 10 Ϫ5 mol/L) and arachidonic acid (10 Ϫ9 to 10 Ϫ5 mol/L) were significantly potentiated in basilar arteries from rabbits injected with AdBDNF. Potentiation of relaxations to acetylcholine in AdBDNF-treated basilar arteries was inhibited by the nonselective cyclooxygenase inhibitor, indomethacin (10 Ϫ5 mol/L, PϽ0.05, nϭ6) and constitutive phospholipase A 2 inhibitor, AACOCF3 (2ϫ10 Ϫ5 mol/L, PϽ0.05, nϭ5). Conclusion-Our

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Section: Discussionsupporting

confidence: 92%

Brain-Derived Neurotrophic Factor Stimulates Production of Prostacyclin in Cerebral Arteries

Santhanam

Smith

Katušić

2010

Stroke

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“…5-HT stimulates endothelial nitric oxide synthase, causing the release of nitric oxide and other labile compounds that relax smooth muscle. It has also been reported to stimulate the release of a vasoconstrictive eicosanoid from the endothelium (30). In addition, 5-HT has been shown to be a type B vasoconstrictor in skeletal muscle.…”

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confidence: 99%

Portal Serotonin Infusion and Glucose Disposal in Conscious Dogs

Moore

Geho²,

Lautz

et al. 2004

Diabetes

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P oor control of postprandial glycemia in type 2 diabetes is associated with elevated rates of all-cause mortality (1), making postprandial hyperglycemia an attractive pharmaceutical target. Individuals who have type 2 diabetes and receive monoamine oxidase inhibitors demonstrate more frequent episodes of hypoglycemia (2), and those who take selective serotonin reuptake inhibitors have improved glucose tolerance (3) compared with similar individuals who do not take these drugs. Moreover, intraperitoneal administration of serotonin (5-hydroxytryptamine [5-HT]) or its precursor 5-hydroxytryptophan has a hypoglycemic effect in mice (4). 5-HT accumulated in both the liver and the brain of the mice, leaving a question of which tissue was responsible for the hypoglycemia. However, in subsequent studies, the mice were also treated with carbidopa, an inhibitor of peripheral but not central aromatic amino acid decarboxylase. Neither hypoglycemia nor hepatic accumulation of 5-HT was observed in carbidopa-treated mice, although brain levels of 5-HT were even higher than in the absence of carbidopa. Thus, it seemed that hypoglycemia was related to the elevation of hepatic 5-HT (5). We hypothesized that 5-HT can reduce postprandial glycemia by enhancing NHGU and examined this hypothesis in conscious dogs in which the pancreatic hormones and hepatic glucose load (HGL) could be fixed. RESEARCH DESIGN AND METHODSAnimals and surgical procedures. Studies were carried out on 16 conscious 42-h-fasted mongrel dogs of either sex with a mean weight of 24 Ϯ 1 kg. Diet and housing were as previously described (6), and the protocol was approved by the Vanderbilt University Medical Center Animal Care Committee.Approximately 16 days before study, each dog underwent a laparotomy for placement of ultrasonic flow probes around the portal vein and the hepatic artery, as well as for insertion of silicone rubber catheters for sampling in a hepatic vein, the portal vein, and a femoral artery and for infusion into a splenic and a jejunal vein as described in detail elsewhere (6,7). Criteria for study were as previously described (6,7).On the morning of the study, catheters and flow probe leads were exteriorized from their subcutaneous pockets (6,7). The splenic and jejunal catheters were used for intraportal infusion of insulin (Eli Lilly & Co., Indianapolis, IN), glucagon (GlucaGen; Bedford Laboratories, Bedford, OH), and 5-HT (5-HT creatinine sulfate complex; Sigma, St. Louis, MO). Angiocaths (Deseret Medical, Sandy, UT) were inserted into three peripheral veins. Experimental design. Each experiment consisted of a 90-min equilibration period (Ϫ120 to Ϫ30 min), a 30-min basal period (Ϫ30 to 0 min), and a 270-min experimental period (0 to 270 min) divided into four subperiods (P1, 0 -90 min; P2, 90 -150 min; P3, 150 -210 min, and P4, 210 -270 min). At Ϫ120 min, a primed, continuous infusion of [3-3 H]glucose and a continuous infusion of indocyanine green dye (5 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were begun in all dogs, with the exception of two that did not re...

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“…In the major cerebral arteries there is good evidence that NO is by far the major mediator of ACh-induced relaxation [66]. This is likely also to be the case in the FA since most large conduit arteries investigated appear to depend essentially on endothelial NO for their relaxation.…”

Section: Discussionmentioning

confidence: 99%

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Kacem¹,

Sercombe²,

Hammami

et al. 2006

J Vasc Res

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Previously [Histochem J 1997;29:279–286], we found that sympathectomy induced neointima formation in ear but not cerebral arteries of genetically hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in atherosclerosis, and whether their influence involves vascular NO activity, we studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6-hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries were studied histochemically, to evaluate differentiation (anti-desmin, anti-vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in vitro myography. In BAs, staining of NI and NS groups was similar. In hypercholesterolemic groups, a small neointima developed, more frequently in HS segments where smooth muscle cells (SMCs) positive for all antibodies appeared to be migrating into the neointima. In FAs, SMCs stained for the three antibodies in the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive cells in some external medial layers of the NS, HI and HS groups, identical to adventitial fibroblasts. Large neointimas of the HS group contained vimentin-positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus, sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate, increasing atherosclerotic lesions, without decreasing NO activity, but has only minor effects on BAs.

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Critical Role of Endothelial Nitric Oxide Synthase and Cyclooxygenase in Response of Rabbit Basilar Artery to Serotonin

Cited by 10 publications

References 47 publications

Brain-Derived Neurotrophic Factor Stimulates Production of Prostacyclin in Cerebral Arteries

Brain-Derived Neurotrophic Factor Stimulates Production of Prostacyclin in Cerebral Arteries

Portal Serotonin Infusion and Glucose Disposal in Conscious Dogs

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

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