Role of nitric oxide in the recovery period after histamine treatment

Persistent Link:
http://hdl.handle.net/10150/284053
Title:
Role of nitric oxide in the recovery period after histamine treatment
Author:
Al-Naemi, Hamda Abdulla
Issue Date:
1999
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Small amounts of nitric oxide are released by endothelial cells under normal physiological conditions whereas, excess amounts are released under inflammatory conditions. Histamine is one of the inflammatory mediators that increases venular permeability to water and proteins. However, the increase in venular permeability that is caused by histamine is transient, and recovers to control levels even with histamine present. The permeability recovery phenomenon suggests a control mechanism that limits the histamine insult. This dissertation research was to investigate the role of nitric oxide in this recovery period after histamine injury. The research was performed to test the hypothesis that nitric oxide is the physiological molecule that counteracts the destructive effect of histamine. Therefore, the role was investigated by using a nitric oxide synthase inhibitor to suppress the production of nitric oxide during the recovery period. The rat mesenteric microvascular network was suffused with histamine for three minutes followed by fifteen minutes of nitric oxide synthase inhibition. It was found that inhibition of nitric oxide production during the recovery period exaggerated the histamine induced venular leaks, and caused further degranulation of mast cells that was stimulated with histamine suffusion. Nitric oxide presence during the recovery period attenuated venular leaks so they fell toward control levels, and prevented further mast cell degranulation. Availability of nitric oxide, via a nitric oxide donor, in venules before histamine suffusion prevented these venules against histamine induced leakage, but it had little effect on mast cell degranulation. An electron microscopic study was performed to further investigate the role of nitric oxide in the recovery period and to test the hypothesis that nitric oxide will be localized to the cell membrane. The immuno-electron microscopic results demonstrated that both number of sites and location of nitric oxide synthase were affected by histamine treatment. There was relocalization of nitric oxide synthase onto the venular endothelia cell surface. Therefore, we concluded that nitric oxide has a direct effect on venular endothelial cells to reduce venular leaks through regulatory mechanism(s) which may involve intercellular junctions and the cytoskeleton.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Biology, Animal Physiology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Baldwin, Ann L.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleRole of nitric oxide in the recovery period after histamine treatmenten_US
dc.creatorAl-Naemi, Hamda Abdullaen_US
dc.contributor.authorAl-Naemi, Hamda Abdullaen_US
dc.date.issued1999en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractSmall amounts of nitric oxide are released by endothelial cells under normal physiological conditions whereas, excess amounts are released under inflammatory conditions. Histamine is one of the inflammatory mediators that increases venular permeability to water and proteins. However, the increase in venular permeability that is caused by histamine is transient, and recovers to control levels even with histamine present. The permeability recovery phenomenon suggests a control mechanism that limits the histamine insult. This dissertation research was to investigate the role of nitric oxide in this recovery period after histamine injury. The research was performed to test the hypothesis that nitric oxide is the physiological molecule that counteracts the destructive effect of histamine. Therefore, the role was investigated by using a nitric oxide synthase inhibitor to suppress the production of nitric oxide during the recovery period. The rat mesenteric microvascular network was suffused with histamine for three minutes followed by fifteen minutes of nitric oxide synthase inhibition. It was found that inhibition of nitric oxide production during the recovery period exaggerated the histamine induced venular leaks, and caused further degranulation of mast cells that was stimulated with histamine suffusion. Nitric oxide presence during the recovery period attenuated venular leaks so they fell toward control levels, and prevented further mast cell degranulation. Availability of nitric oxide, via a nitric oxide donor, in venules before histamine suffusion prevented these venules against histamine induced leakage, but it had little effect on mast cell degranulation. An electron microscopic study was performed to further investigate the role of nitric oxide in the recovery period and to test the hypothesis that nitric oxide will be localized to the cell membrane. The immuno-electron microscopic results demonstrated that both number of sites and location of nitric oxide synthase were affected by histamine treatment. There was relocalization of nitric oxide synthase onto the venular endothelia cell surface. Therefore, we concluded that nitric oxide has a direct effect on venular endothelial cells to reduce venular leaks through regulatory mechanism(s) which may involve intercellular junctions and the cytoskeleton.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectBiology, Animal Physiology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBaldwin, Ann L.en_US
dc.identifier.proquest9960253en_US
dc.identifier.bibrecord.b40274263en_US
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