Endothelium and the effect of activated neutrophils on arterial smooth muscle

Abstract The aim of the study was to analyze the involvement of the endothelium in the effects of neutrophils (PMNL) on phenylephrine-pre-contracted isolated rings of the rat thoracic aorta and to compare their effects with those of peroxynitrite (ONOO−) and hypochlorous acid (HOCl). Activated PMNL-induced contraction of the precontracted aorta was prevented by the blockade of NO-synthase and by endothelium removal. In the endothelium-free preparations, the effect of PMNL reappeared in the presence of sodium nitroprusside. The effect of ONOO− and HOCl significantly differed from that of activated PMNL both in the presence and absence of the endothelium. It is therefore likely that neither ONOO− nor HOCl generated by transformation of superoxide anion radical (O2•−) produced by PMNL is involved in their action. Reduction of the relaxant effect of nitric oxide derived from the endothelium by O2•− seems to be the keystone mechanism in generation of PMNL-induced contraction.

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Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.262.4.g774 ◽

1992 ◽

Vol 262 (4) ◽

pp. G774-G778 ◽

Cited By ~ 18

Author(s):

J. R. Grider ◽

K. S. Murthy ◽

J. G. Jin ◽

G. M. Makhlouf

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Muscle Cells ◽

No Synthase ◽

No Production ◽

Field Stimulation ◽

Relaxant Effect ◽

Gastric Muscle ◽

Synthase Inhibitor ◽

Stimulation Of

The source of nitric oxide (NO) and its role in neurally induced relaxation was examined in smooth muscle of the stomach and tenia coli. Field stimulation of gastric muscle strips was accompanied by frequency-dependent relaxation, vasoactive intestinal peptide (VIP) release, and NO production: the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA) completely inhibited NO production and partly inhibited VIP release (52-54%) and relaxation (58-88%); inhibition of all three functions was reversed by L-arginine but not by D-arginine. In isolated gastric muscle cells, VIP caused relaxation and stimulated NO production: L-NNA completely inhibited NO production and partly inhibited relaxation; the inhibition was reversed by L-arginine but not by D-arginine. Abolition of NO production with only partial inhibition of relaxation implied that NO production from muscle cells induced by the action of VIP was partly responsible for relaxation. By contrast, field stimulation of tenia coli was accompanied by relaxation and VIP release but not by NO production. Neither VIP release nor relaxation was affected by L-NNA. In isolated muscle cells of tenia coli, VIP caused relaxation but did not stimulate NO production; relaxation in these cells was not affected by L-NNA. We conclude that 1) VIP is the primary relaxant transmitter in both gastric muscle and tenia coli, 2) the release of VIP in gastric muscle but not in tenia coli stimulates NO production from target muscle cells, and 3) NO amplifies the relaxant effect of VIP in muscle cells and acts presynaptically to enhance the release of VIP.

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Antioxidant Activities of Imino Chromene Derivatives with Even Alkyl tail: Synthesis and Characterisation

International Journal of Innovative Technology and Exploring Engineering - Special Issue ◽

10.35940/ijitee.b1119.1292s419 ◽

2019 ◽

Vol 9 (2S4) ◽

pp. 211-213

Keyword(s):

Nitric Oxide ◽

Superoxide Anion ◽

Anion Radical ◽

Antioxidant Activities ◽

Natural Antioxidants ◽

Dpph Radical ◽

Nitric Oxide Radical ◽

Active Methylene Compounds ◽

Active Methylene ◽

Alkyl Tail

The reaction between substituted 4-hydroxybenzaldehyde, active methylene compounds iminochromene derivatives. Structures of the sewere established upon the basis of IR,1HNMR,13CNMR,and MASS data. Invitro, antioxidants activities oft hese compounds against superoxide anion radical, nitric oxide radical, DPPH radical and hydrogen peroxide were evaluated and compared with standard natural antioxidants ascorbicacid.

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Interplay of VIP and nitric oxide in regulation of the descending relaxation phase of peristalsis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.2.g334 ◽

1993 ◽

Vol 264 (2) ◽

pp. G334-G340 ◽

Cited By ~ 23

Author(s):

J. R. Grider

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Protein Kinase ◽

Protein Kinase G ◽

Rat Colon ◽

No Production ◽

Field Stimulation ◽

Relaxant Effect ◽

Relaxation Phase ◽

Kinase A

Involvement of vasoactive intestinal peptide (VIP) and nitric oxide (NO) in neurally induced relaxation was examined in smooth muscle from rat colon. Relaxation induced by field stimulation or radial stretch (i.e., descending relaxation phase of the peristaltic reflex) was accompanied by VIP release and NO production. NG-nitro-L-arginine (L-NNA) abolished NO production in both preparations but only partly inhibited VIP release (45 +/- 8% at 8 Hz and 59 +/- 10% at 10 g stretch) and relaxation (62 +/- 5% and 35 +/- 6%); the effect of L-NNA was reversed by L-arginine but not D-arginine. The pattern implied that NO production normally acts to enhance VIP release. In addition, VIP induced relaxation and stimulated NO production in muscle strips and isolated colonic muscle cells: L-NNA abolished NO production but only partly inhibited relaxation (58 +/- 6%); oxyhemoglobin had no effect. The effect of L-NNA on relaxation was reversed by L-arginine but not by D-arginine. The protein kinase A inhibitor (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS] and the protein kinase G inhibitor KT5823 inhibited VIP-induced relaxation by 76 +/- 5 and 35 +/- 4%, respectively; a combination of the two inhibitors abolished relaxation. (R)-p-cAMPS blocked the direct relaxant effect of VIP, whereas KT5823 blocked the indirect effect of VIP mediated by NO.(ABSTRACT TRUNCATED AT 250 WORDS)

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Adenosine receptor-mediated relaxation of rabbit airway smooth muscle: a role for nitric oxide

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.273.3.l581 ◽

1997 ◽

Vol 273 (3) ◽

pp. L581-L587 ◽

Cited By ~ 6

Author(s):

S. Ali ◽

W. J. Metzger ◽

H. A. Olanrewaju ◽

S. J. Mustafa

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Epithelial Cells ◽

Airway Smooth Muscle ◽

Adenosine Receptor ◽

Inhibitory Effect ◽

No Production ◽

Relaxant Effect ◽

Adenosine Receptor Agonists ◽

Cgs 21680

In this study, we investigated the relaxant effect of adenosine receptor agonists on KCl-precontracted airway smooth muscle from rabbits and characterized the type of receptor involved in bronchorelaxation in the presence and absence of epithelium. We further defined the role of epithelium-derived relaxing factor, i.e., nitric oxide (NO), on these responses. In both epithelium-intact and -denuded tertiary airway rings from rabbits, the adenosine receptor agonists 2-[p-(2-carboxyethyl)]phenylethylamino-5-N'-ethylcarboxamidoadenos ine (CGS-21680), 5'-(N-ethyl-carboxamido)adenosine (NECA), 2-chloroadenosine (CAD), and (-)-N6-(2-phenylisopropyl)adenosine (R-PIA) relaxed airway smooth muscle with a potency order of CGS-21680 > NECA > CAD > R-PIA. A 98.5, 89.7, 73.2, and 64.7% relaxation was observed at 10(-5) M by CGS-21680, NECA, CAD, and R-PIA in the epithelium-intact bronchial rings, respectively. The 50% maximum effective concentration (EC50; x 10(-7) M) values for CGS-21680, NECA, CAD, and R-PIA were 2, 4, 9, and 80, respectively. Denuded rings, however, showed much less relaxant responses to various adenosine agonists compared with epithelium-intact rings. The adenosine receptor antagonist 8-(sulfophenyl)theophylline significantly attenuated the relaxant responses to all the agonists in the epithelium-intact and -denuded rings. The epithelium-dependent relaxant effect of the agonists in airway rings was inhibited by NG-monomethyl-L-arginine (L-NMMA; 30 microM). The EC50 (x 10(-6) M) values for CGS-21680, NECA, CAD, and R-PIA in the presence of inhibitor were 5.5, 8, 30, and 200, respectively. The L-NMMA produced an insignificant inhibitory effect in the epithelium-denuded rings. L-Arginine but not D-arginine (100 microM) reversed the inhibitory effect of L-NMMA on adenosine agonist-induced relaxation. In primary epithelial cells in culture, CGS-21680 (10(-5) M) induced a fourfold increase in NO production over the control. The CGS-21680-induced NO production in epithelial cells was significantly inhibited by NG-nitro-L-arginine methyl ester (L-NAME). Moreover, L-arginine reversed the inhibitory effect of L-NAME in the epithelial cells. The data suggest that adenosine relaxes rabbit airway smooth muscle through an A2 adenosine receptor and the epithelium serves as a source of NO.

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Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies

AJP Cell Physiology ◽

10.1152/ajpcell.1993.265.5.c1379 ◽

1993 ◽

Vol 265 (5) ◽

pp. C1379-C1387 ◽

Cited By ~ 136

Author(s):

J. S. Pollock ◽

M. Nakane ◽

L. D. Buttery ◽

A. Martinez ◽

D. Springall ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Smooth Muscle ◽

Monoclonal Antibodies ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

No Synthase ◽

Endothelial No Synthase ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

We have produced specific monoclonal antibodies (MAb) against particulate bovine aortic endothelial nitric oxide synthase. In Western blots, native and cultured bovine aortic endothelial cells as well as cultured bovine microvascular endothelial cells possess immunoreactive NO synthase. In dot blots, MAb H210 and H32 detect 1 ng and 100 pg of purified endothelial NO synthase, respectively. Both antibodies are specific to the endothelial NO synthase and do not cross-react with other known isoforms of NO synthase, namely from the brain, from cytokine/endotoxin-induced macrophages, or from cytokine/endotoxin-induced vascular smooth muscle cells. Immunohistochemical studies demonstrated the specificity of endothelial NO synthase for endothelial cells in various bovine and human tissues. Many types of endothelial cells, macrovascular, microvascular, arterial, and venous were found to possess this specific isoform of NO synthase. Electron microscopy showed the enzyme to be associated with the plasma membrane, membranes of cytoplasmic vesicles, and in the cytoplasm in human umbilical vein endothelial cells. The results demonstrate that particulate endothelial NO synthase is present in a site to act rapidly to produce NO for release into the blood or toward the smooth muscle in many vascular beds.

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Superoxide Anion From the Adventitia of the Rat Thoracic Aorta Inactivates Nitric Oxide

Circulation Research ◽

10.1161/01.res.82.7.810 ◽

1998 ◽

Vol 82 (7) ◽

pp. 810-818 ◽

Cited By ~ 237

Author(s):

Hui Di Wang ◽

Patrick J. Pagano ◽

Yue Du ◽

Antonio J. Cayatte ◽

Mark T. Quinn ◽

...

Keyword(s):

Nitric Oxide ◽

Thoracic Aorta ◽

Superoxide Anion ◽

Rat Thoracic Aorta

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Role of K+Channels in Augmented Relaxations to Sodium Nitroprusside Induced by Mexiletine in Rat Aortas

Anesthesiology ◽

10.1097/00000542-200003000-00025 ◽

2000 ◽

Vol 92 (3) ◽

pp. 813-820 ◽

Cited By ~ 12

Author(s):

Hiroyuki Kinoshita ◽

Toshizo Ishikawa ◽

Yoshio Hatano

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Sodium Nitroprusside ◽

Guanylate Cyclase ◽

Nitric Oxide Donor ◽

Nitric Oxide Donors ◽

K Channels ◽

Vasodilator Effect ◽

Isolated Rat

Background A class Ib antiarrhythmic drug, mexiletine, augments relaxations produced by adenosine triphosphate (ATP) sensitive K+ channel openers in isolated rat aortas, suggesting that it produces changes in the vasodilation mediated by ATP-sensitive K+ channels. Nitric oxide can induce its vasodilator effect via K+ channels, including ATP-sensitive K+ channels, in smooth muscle cells. Effects of mexiletine on arterial relaxations to nitric oxide donors, have not been studied. Therefore, the current study in isolated rat aortas was designed to (1) evaluate whether mexiletine augments relaxation in response to nitric oxide donors, including sodium nitroprusside, and (2) determine the role of K+ channels in mediating effects of mexiletine on such nitric oxide-mediated relaxation. Methods Rings of rat aortas without endothelia were suspended for isometric force recording. Concentration-response curves of sodium nitroprusside (10(-10) to 10(-5) M) and 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-9) to 10(-5) M) were obtained in the absence and in the presence of mexiletine, in combination with a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one (ODQ), or inhibitors for ATP-sensitive K+ channels (glibenclamide), inward rectifier K+ channels (BaCl2), delayed rectifier K+ channels (4-aminopyridine), large conductance Ca2+-dependent K+ channels (iberiotoxin), or small conductance Ca2+-dependent K+ channels (apamin). Results Mexiletine (10(-5) or 3 x 10(-5) M) augmented relaxations to sodium nitroprusside and NOC-7. In arteries treated with glibenclamide (10(-5) M), mexiletine (3 x 10(-5) M) did not affect relaxations to nitric oxide donors, whereas mexiletine augmented relaxations to sodium nitroprusside despite the presence of BaCl2 (10(-5) M), 4-aminopyridine (10(-3) M), iberiotoxin (5 x 10(-8) M) and apamin (5 x 10(-8) M). Relaxations to sodium nitroprusside were abolished by ODQ (5 x 10(-6) M), whereas these relaxations were augmented by mexiletine (3 x 10(-5) M) in arteries treated with ODQ (5 x 10(-6) M). Conclusions These results suggest that ATP-sensitive K+ channels in vascular smooth muscle, contribute to the augmented vasodilator effect of a nitric oxide donor, sodium nitroprusside induced by mexiletine, and that the vasodilator effect is produced, at least in part, via the guanylate cyclase-independent mechanism.

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