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.

Endothelial vasoconstrictor prostanoids modulate contractions to acetylcholine and ANG II in Ren-2 rats

1997 ◽  
Vol 272 (1) ◽  
pp. H493-H500 ◽  
Author(s):  
G. Noll ◽  
M. G. Lang ◽  
M. R. Tschudi ◽  
D. Ganten ◽  
T. F. Luscher
Keyword(s):  
Angiotensin Ii ◽  
Vascular Function ◽  
Tissue Perfusion ◽  
Isometric Tension ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Angiotensin I ◽  
Transgenic Rats ◽  
Endothelin 1 ◽  
Thromboxane Receptor Antagonist

We investigated vascular function in mouse Ren-2 transgenic rats with hypertension. Mesenteric resistance arteries of transgenic and Sprague-Dawley rats (controls) were isolated at ages 6 and 12 wk and suspended in myographs for isometric tension recording. Systolic blood pressure was higher in transgenic than control rats (P < 0.05). Contractions to norepinephrine and endothelin-1 were comparable in transgenic and control rats, but the sensitivity decreased with age in both strains (P < 0.05). Contractions to angiotensin I were comparable in 6-wk-old transgenic rats and controls, but the response to angiotensin I was more pronounced in transgenic rats at 12 wk of age. Contractions to angiotensin II were higher in transgenic rats and decreased with age in both strains. Preincubation with the cyclooxygenase inhibitor meclofenamate or the thromboxane receptor antagonist SQ-30741 blunted the response only in 6-wk-old transgenic rats. In quiescent vascular rings, acetylcholine evoked endothelium-dependent contractions after inhibition of nitric oxide formation by N omega-nitro-L-arginine methyl ester only in transgenic rats. These contractions were inhibited by SQ-30741 (P < 0.05) but not by the thromboxane synthase inhibitor CGS-13080. Contractions to the thromboxane analogue U-46619 were comparable in both strains at the age of 6 wk; sensitivity was increased in transgenic rats at 12 wk (P < 0.05). In conclusion, in mesenteric resistance arteries of Ren-2 transgenic rats I) contractions to angiotensin I and II but not to norepinephrine and endothelin-1 are increased, and 2) acetylcholine as well as angiotensin II modulate endothelium-dependent contractions mediated by prostaglandin H2. These alterations together with increased sensitivity to thromboxane could contribute to maintenance as well as to impaired tissue perfusion of this form of hypertension.

scholarly journals Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE

2009 ◽  
Vol 297 (4) ◽  
pp. F875-F884 ◽  
Author(s):  
Kazuyoshi Inoue ◽  
Komal Sodhi ◽  
Nitin Puri ◽  
Katherine H. Gotlinger ◽  
Jiang Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Renal Injury ◽  
Vascular Function ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have previously reported that adenoviral-mediated delivery of cytochrome P-450 (CYP) 4A2, which catalyzes the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), results in endothelial dysfunction and hypertension in Sprague-Dawley (SD) rats (Wang JS, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, Wolin MS, Hintze TH, Abraham NG, Nasjletti A, Laniado-Schwartzman M. Circ Res 98: 962–969, 2006). In this study, we targeted the vascular endothelium by using a lentivirus construct expressing CYP4A2 under the control of the endothelium-specific promoter VE-cadherin (VECAD-4A2) and examined the effect of long-term CYP4A2 overexpression on blood pressure and kidney function in SD rats. A bolus injection of VECAD-4A2 increased blood pressure ( P < 0.001) by 26, 36, and 30 mmHg 10, 20, and 30 days postinjection, respectively. Arteries from VECAD-4A2-transduced rats produced increased levels of 20-HETE ( P < 0.01), expressed lower levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) ( P < 0.05), generated higher levels of superoxide anion, and displayed decreased relaxing responsiveness to acetylcholine ( P < 0.05). Proteinuria increased by twofold in VECAD-4A2-transduced rats compared with controls. Treatment of VECAD-4A2-transduced rats with HET0016, an inhibitor of 20-HETE biosynthesis, not only attenuated the increase in blood pressure ( P < 0.05) but also improved vascular function (acetylcholine-induced relaxations) and reduced plasma creatinine and proteinuria. HET0016 treatment decreased oxidative stress and increased the phosphorylated state of key proteins that regulate endothelial function, including eNOS, AKT, and AMPK. Collectively, these findings demonstrate that augmentation of vascular endothelial 20-HETE levels results in hypertension, endothelial dysfunction, and renal injury, which is offset by HET0016 through a reduction in vascular 20-HETE coupled with a lessening of oxidative stress and the amplification of pAKT, pAMPK, and p-eNOS levels leading to normalization of endothelial responses.

Role of Cl− current in endothelin-1-induced contraction in rabbit basilar artery

2001 ◽  
Vol 281 (5) ◽  
pp. H2159-H2167 ◽  
Author(s):  
Yun Dai ◽  
John H. Zhang
Keyword(s):  
Basilar Artery ◽  
Methanesulfonic Acid ◽  
Isometric Tension ◽  
Channel Blockers ◽  
Free Solution ◽  
Bicarbonate Buffer ◽  
Endothelin 1 ◽  
New Zealand White Rabbits ◽  
Basilar Arteries

Cl− efflux induces depolarization and contraction of smooth muscle cells. This study was undertaken to explore the role of Cl− channels in endothelin-1 (ET-1)-induced contraction in rabbit basilar artery. Male New Zealand White rabbits ( n = 26), weighing 1.8–2.5 kg, were euthanized by an overdose of pentobarbital. The basilar arteries were removed for isometric tension recording. ET-1 produced a concentration-dependent contraction of the rabbit basilar artery in the normal Cl− Krebs-Henseleit bicarbonate buffer (123 mM Cl−). The ET-1-induced contraction was reduced by the following manipulations: 1) inhibition of Na+-K+-2Cl− cotransporter with bumetanide (3 × 10−5 and 10−4 M), 2) bicarbonate-free solution to disable Cl−/HCO[Formula: see text] exchanger, and 3) preincubation of rings with the Cl− channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and indanyloxyacetic acid 94. The ET-1-induced contraction was enhanced by substitution of extracellular Cl− (10 mM) with methanesulfonic acid (113 mM). Cl− channels are involved in ET-1-induced contraction in the rabbit basilar artery.

scholarly journals Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Seonhee Kim ◽  
Ikjun Lee ◽  
Hee-Jung Song ◽  
Su-jeong Choi ◽  
Harsha Nagar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vascular Function ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Diseases ◽  
Far Infrared ◽  
No Production ◽  
Sprague Dawley ◽  
Endothelial Nitric Oxide

Far-infrared ray (FIR) therapy has been reported to exert beneficial effects on cardiovascular function by elevating endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) production. Tetrahydrobiopterin (BH4) is a key determinant of eNOS-dependent NO synthesis in vascular endothelial cells. However, whether BH4 synthesis is associated with the effects of FIR on eNOS/NO production has not yet been investigated. In this study, we investigated the effects of FIR on BH4-dependent eNOS/NO production and vascular function. We used FIR-emitting sericite boards as an experimental material and placed human umbilical vein endothelial cells (HUVECs) and Sprague–Dawley rats on the boards with or without FIR irradiation and then evaluated vascular relaxation by detecting NO generation, BH4 synthesis, and Akt/eNOS activation. Our results showed that FIR radiation significantly enhanced Akt/eNOS phosphorylation and NO production in human endothelial cells and aorta tissues. FIR can also induce BH4 storage by elevating levels of enzymes (e.g., guanosine triphosphate cyclohydrolase-1, 6-pyruvoyl tetrahydrobiopterin synthase, sepiapterin reductase, and dihydrofolate reductase), which ultimately results in NO production. These results indicate that FIR upregulated eNOS-dependent NO generation via BH4 synthesis and Akt phosphorylation, which contributes to the regulation of vascular function. This might develop potential clinical application of FIR to treat vascular diseases by augmenting the BH4/NO pathway.

scholarly journals Upregulation of Relaxin after Experimental Subarachnoid Hemorrhage in Rabbits

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yuichiro Kikkawa ◽  
Satoshi Matsuo ◽  
Ryota Kurogi ◽  
Akira Nakamizo ◽  
Masahiro Mizoguchi ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Messenger Rna ◽  
Cerebral Arteries ◽  
Enzyme Linked Immunosorbent Assay ◽  
Endothelin 1 ◽  
Basilar Arteries ◽  
Experimental Subarachnoid Hemorrhage

Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in rabbits.Methods. Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1) was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF) and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC) preincubated with relaxin, myosin light chain phosphorylation (MLC) was investigated with immunoblotting after endothelin-1 stimulation.Results. After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC.Conclusion. Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm.

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 Adventitial Expression of Recombinant Endothelial Nitric Oxide Synthase Gene Reverses Vasoconstrictor Effect of Endothelin-1

1999 ◽  
Vol 19 (9) ◽  
pp. 1029-1037 ◽  
Author(s):  
Hisashi Onoue ◽  
Masato Tsutsui ◽  
Leslie Smith ◽  
Timothy O'Brien ◽  
Zvonimir S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Receptor Antagonist ◽  
Endothelial Nitric Oxide Synthase ◽  
Ex Vivo ◽  
Enos Gene ◽  
Endothelin 1 ◽  
Basilar Arteries ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The present study was designed to determine the effect of recombinant endothelial nitric oxide synthase (eNOS) gene expression on reactivity of canine basilar arteries to endothelin-1 (ET-1). Experiments were performed ex vivo. The arteries were exposed (30 minutes at 37°C) to adenoviral vectors encoding eNOS gene (AdCMVeNOS) or β-galactosidase reporter gene (AdCMVβ-Gal). Twenty-four hours after transduction, transgene expression was evident mainly in the vascular adventitia. Rings of control (nontransduced), AdCMVβ-Gal- and AdCMVeNOS-transduced arteries with and without endothelium were suspended for isometric tension recording. Levels of guanosine 3′,5′ -cyclic monophosphate (cGMP) were measured by radioimmunoassay. During contractions to uridine 5′-triphosphate, ET-1 (10−10 to 3×10−9 mol/L) caused further increase in tension in control and AdCMVβ-Gal-transduced arteries. In contrast, ET-1 caused concentration-dependent relaxations of AdCMVeNOS-transduced arteries. The relaxations to ET-1 in AdCMVeNOS-transduced arteries were endothelium-independent They were abolished by NG-nitro-L-argininemethyl ester or by chemical treatment of adventitia with paraformaldehyde before gene transfer. ET-1 (10−9 mol/L) significantly increased intracellular cGMP levels in AdCMVeNOS-transduced arteries without endothelium. In arteries transduced with AdCMVeNOS, higher concentrations (10−9 to 3×10−8 mol/L) of ET-2 also caused relaxations, whereas ET-3 and sarafotoxin, a selective ETB receptor agonist, did not produce any relaxations. The relaxations to ET-1 in AdCMVeNOS-transduced arteries were strongly reduced by BQ-123 (10−7 mol/L), an ETA receptor antagonist, but were not affected by BQ-788 (3×10−7 mol/L), an ETB receptor antagonist These results suggest that genetically modified adventitia can produce nitric oxide and cause relaxations in response to ET-1 via activation of ETA receptors. Our findings support a novel concept that successful transfer and expression of recombinant eNOS gene can lead to a qualitative change in responsiveness to vasoconstrictor substances.

scholarly journals Food Restriction Augmented Alpha1 Adrenergic Mediated Contraction in Mesenteric Arteries

2021 ◽  
Author(s):  
Rany Vorn ◽  
Hae Young Yoo
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Vascular Function ◽  
Food Restriction ◽  
Vascular Reactivity ◽  
Hypovolemic Shock ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Underlying Mechanisms ◽  
Endothelial Nitric Oxide

Food restriction (FR) enhances the sensitivity to cardiopulmonary reflexes and alpha1 adrenoreceptors in the female, despite hypotension. The effect of male FR on cardiopulmonary and systemic vascular function is not well understood. This study examines the effects of FR on cardiopulmonary, isolated mesenteric arterial function and potential underlying mechanisms. We hypothesized that FR decreased eNOS activity in mesenteric arteries. Male Sprague Dawley (SD) rats were randomly divided into three groups: (1) control (n=30), (2) 20 percent of food reduction (FR20, n=30), and (3) 40 percent of food reduction (FR40, n=30) for five weeks. Non-invasive blood pressure was measured twice a week. Pulmonary arterial pressure (PAP) was measured using isolated/perfused lungs in rats. The isolated vascular reactivity was assessed in double-wire myograph. After five weeks, food restricted rats exhibited a lower mean arterial pressure and heart rate, however, only FR40 groups exhibited statistically significant differences. The basal tone of PAP and various vasoconstrictors did not show significant differences in pulmonary circulation between each group. We observed that food restriction were enhanced the sensitivity (EC50) in response to α1-adrenoreceptors (phenylephrine, PhE)-induced vasoconstriction, but not to serotonin, U46619, and high K+ in the mesenteric arteries. FR reduced endothelium-dependent relaxation via decreased function of endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) pathway in the mesenteric arteries. PhE-mediated vasoconstriction in mesenteric arteries was eliminated in the presence of eNOS inhibitor (L-NAME). In addition, incubation with NOX2/4 inhibitors (apocynin, GKT137831, VAS2870) and reactive oxygen species (ROS) scavenger inhibitor (Tiron) were eliminated the differences of PhE-mediated vasoconstriction but not to cyclooxygenase inhibitor (indomethacin) in the mesenteric artery. Augmentation of alpha1 adrenergic mediated contraction via inhibition of eNOS-NO pathway by increased activation of ROS through NOX2/4 in response to FR. Reduced eNOS-NO signaling might be a pathophysiological counterbalance to prevent hypovolemic shock in response to FR.

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