Endothelial expression of selectins during endotoxin preconditioning

Although bacterial endotoxins [lipopolysaccharide (LPS)] can confer tissue resistance to subsequent inflammatory insults, the mechanisms that underlie this LPS-preconditioning (LPS-PC) response remain poorly defined. The dual-radiolabeled monoclonal antibody technique was used to examine whether LPS-PC alters the upregulation (protein) of E- and P-selectins after subsequent LPS challenge. In the gut of wild-type (C57BL/6J) mice, LPS-PC was associated with a reduction in E- (66%) and P-selectin (33%) expression. A similar reduction in E-selectin expression was observed in mutant mice that were genetically deficient in either the endothelial or inducible isoform of nitric oxide synthase or that overexpressed the human gene for Cu/Zn superoxide dismutase. Severe combined immunodeficient mice, genetically devoid of lymphocytes, did exhibit partial inhibition of the LPS-PC response. We conclude that 1) LPS-PC can be demonstrated for E- and P-selectins in some vascular beds (e.g., gut), 2) the mechanism(s) underlying this blunted selectin response does not include a major role for either nitric oxide and superoxide, and 3) circulating lymphocytes may contribute to the LPS-PC response.

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Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00110.2015 ◽

2015 ◽

Vol 309 (2) ◽

pp. R189-R195 ◽

Cited By ~ 14

Author(s):

Mercedes Perusquía ◽

Clayton D. Greenway ◽

Lisa M. Perkins ◽

John N. Stallone

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Sprague Dawley ◽

Peripheral Vasculature ◽

Similar Reduction ◽

Arterial Blood ◽

Sd Rats ◽

Oxide Synthase

Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16–20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375–6.00 μmol·kg−1·min−1 iv; 10 min/dose). Data are expressed as means ± SE ( n = 5–8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg−1·min−1, iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30–40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg−1·min−1 × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

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Chlorpromazine Inhibits Both the Constitutive Nitric Oxide Synthase and the Induction of Nitric Oxide Synthase After LPS Challenge

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1993.2246 ◽

1993 ◽

Vol 196 (1) ◽

pp. 280-286 ◽

Cited By ~ 29

Author(s):

M. Palacios ◽

J. Padron ◽

L. Glaria ◽

A. Rojas ◽

R. Delgado ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Lps Challenge ◽

Constitutive Nitric Oxide Synthase ◽

Oxide Synthase

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Role of inducible nitric oxide synthase in the regulation of VCAM-1 expression in gut inflammation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.3.g572 ◽

1999 ◽

Vol 277 (3) ◽

pp. G572-G576 ◽

Cited By ~ 6

Author(s):

Shigeyuki Kawachi ◽

Adam Cockrell ◽

F. Stephen Laroux ◽

Laura Gray ◽

D. Neil Granger ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Wild Type ◽

Chronic Colitis ◽

Antibody Technique ◽

Tnf Α ◽

Factor Α ◽

Oxide Synthase

The objectives of this study were to assess the role of the inducible isoform of nitric oxide synthase (iNOS) on vascular cell adhesion molecule 1 (VCAM-1) expression in vivo in an acute model of inflammation induced in iNOS-deficient (iNOS−/−) mice and compare these data to those obtained by pharmacological inhibition of iNOS in a CD4+ T lymphocyte-dependent model of chronic colitis. VCAM-1 expression was quantified in vivo using the dual radiolabel monoclonal antibody technique. We found that intraperitoneal injection of 10 μg/kg tumor necrosis factor-α (TNF-α) enhanced VCAM-1 expression by approximately twofold in the colon, cecum, and stomach but not small intestine in iNOS−/−mice compared with TNF-α-injected wild-type mice. Injection of wild-type mice with 25 μg/kg TNF-α further enhanced VCAM-1 expression by approximately twofold compared with wild-type mice injected with 10 μg/kg TNF-α; however, VCAM-1 expression was not further enhanced in any gastrointestinal organ system in iNOS−/− mice. In a second series of experiments, we found that continuous inhibition of iNOS using oral administration of N G-iminoethyl-l-lysine did not alter the enhanced levels of VCAM-1 expression in the colon nor did it alter the severity of colonic inflammation in SCID mice reconstituted with CD4+, CD45RBhigh T cells. We conclude that iNOS may regulate VCAM-1 expression in acute inflammation; however, this effect is modest and tissue specific and occurs only when VCAM-1 expression is submaximal. iNOS does not appear to modulate VCAM-1 expression in an immune model of chronic colitis.

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Effects of Nitric Oxide Synthase Inhibition on Cerebral Blood Flow following Bilateral Carotid Artery Occlusion and Recirculation in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.91 ◽

1993 ◽

Vol 13 (4) ◽

pp. 720-723 ◽

Cited By ~ 47

Author(s):

Ricardo Prado ◽

Brant D. Watson ◽

Per Wester

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Carotid Artery ◽

Artery Occlusion ◽

Carotid Artery Occlusion ◽

Similar Reduction ◽

Bilateral Carotid ◽

Bilateral Carotid Artery Occlusion ◽

Oxide Synthase ◽

Bilateral Carotid Artery

The effects of bilateral carotid artery occlusion/recirculation on cortical CBF (cCBF) were studied in rats following the intravenous administration of either the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester hydrochloride (l-NAME; 30 mg/kg) or an equivalent volume of saline (500 μl). Induction of bilateral carotid occlusion (BCO) in l-NAME-treated animals resulted in a reduction of cCBF to 30% of baseline. During recirculation subsequent to 20 min of BCO, cCBF in l-NAME-infused animals remained at 30% of baseline. In contrast, cCBF in saline-treated control animals returned to the original baseline level following a similar reduction to 30–40% of baseline during BCO. These results indicate that inhibition of nitric oxide generation limits normalization of regional cortical perfusion following occlusion of proximal large cerebral vessels.

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Localization of endothelial nitric oxide synthase in the normal and failing human atrial myocardium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166397 ◽

1996 ◽

Vol 54 ◽

pp. 786-787

Author(s):

Chi-Ming Wei ◽

Margarita Bracamonte ◽

Shi-Wen Jiang ◽

Richard C. Daly ◽

Christopher G.A. McGregor ◽

...

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Cardiac Tissues ◽

Mammalian Tissues ◽

End Stage Heart Failure ◽

End Stage ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Nitric oxide (NO) is a potent endothelium-derived relaxing factor which also may modulate cardiomyocyte inotropism and growth via increasing cGMP. While endothelial nitric oxide synthase (eNOS) isoforms have been detected in non-human mammalian tissues, expression and localization of eNOS in the normal and failing human myocardium are poorly defined. Therefore, the present study was designed to investigate eNOS in human cardiac tissues in the presence and absence of congestive heart failure (CHF).Normal and failing atrial tissue were obtained from six cardiac donors and six end-stage heart failure patients undergoing primary cardiac transplantation. ENOS protein expression and localization was investigated utilizing Western blot analysis and immunohistochemical staining with the polyclonal rabbit antibody to eNOS (Transduction Laboratories, Lexington, Kentucky).

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