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dc.contributor.advisor Lokhandwala, Mustafa F.
dc.creator Bhatt, Siddhartha
dc.date.accessioned 2012-04-19T14:27:21Z
dc.date.accessioned 2012-04-19T14:27:23Z
dc.date.available 2012-04-19T14:27:21Z
dc.date.available 2012-04-19T14:27:23Z
dc.date.created 2011-08
dc.date.issued 2012-04-19
dc.date.submitted August 2011
dc.identifier.uri http://hdl.handle.net/10657/271
dc.description.abstract Hypertension affects 1 in 3 adult Americans and is a primary risk factor for cardiovascular diseases. Better understanding of hypertension pathogenesis is important for development of effective therapeutic agents. An important underlying factor present during hypertension is oxidative stress (OS). However, causal role of OS in hypertension is unclear. Increased vascular resistance resulting from enhanced vasoconstriction and impaired vasodilation is a hallmark of hypertension. Enhanced vasoconstriction is associated with increased reactivity to vasoconstrictors such as angiotensin (Ang) II. Ang II-induced vasoconstriction is exaggerated during hypertension and is associated with Ang II type 1 receptors (AT1R) upregulation, the cause of which is unknown. OS modulates redox sensitive transcription factors including nuclear factor kappa B (NFκB), which has been associated with AT1R upregulation. Thus, OS via NFκB can transcriptionally upregulate AT1R. The impaired vasodilation in hypertension is attributed to endothelial dysfunction resulting from attenuated nitric oxide (NO) availability. OS can also contribute to endothelial dysfunction by reducing NO production and increasing NO scavenging. Our objective was to study the role of OS in hypertension development. The first part of the study investigates whether OS is a cause or consequence of hypertension. Studies in 3-4 week old spontaneously hypertensive rats (SHR) revealed that OS precedes hypertension development and is associated with NFκB activation and AT1R upregulation. Treatment of young SHR with pyrrolidine dithiocarbamate, an antioxidant with NFκB inhibitory action, attenuated hypertension development and normalized NFκB and AT1R expression. Experiments in human aortic smooth muscle cells also exhibited OS-induced AT1R upregulation through mechanisms involving NFκB. The second part of the study investigates the role of early oxidative stress in endothelial dysfunction with focus on elucidating role of resveratrol, an antioxidant polyphenol. Our results demonstrate, early resveratrol treatment lowers oxidative stress and reduces NO scavenging and eNOS uncoupling thereby preventing endothelial dysfunction and attenuating hypertension development. In conclusion, early vascular OS in SHR could contribute to hypertension by modulating AT1 receptor upregulation, possibly via NFκB. Additionally, vascular OS could also contribute to endothelial dysfunction by increasing NO scavenging and eNOS uncoupling. Resveratrol treatment lowered oxidative stress, prevented endothelial dysfunction and attenuated hypertension development in SHR.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subject Oxidative stress
dc.subject AT1 Receptors
dc.subject Endothelial Dysfunction
dc.subject Vascular
dc.title Role of Vascular Oxidative Stress in Hypertension
dc.date.updated 2012-04-19T14:27:23Z
dc.type.material text *
dc.type.genre thesis *
thesis.degree.name Pharmacology
thesis.degree.level Doctoral
thesis.degree.discipline Pharmacology
thesis.degree.grantor University of Houston
thesis.degree.department Pharmacological and Pharmaceutical Sciences
dc.contributor.committeeMember Banday, Anees Ahmad
dc.contributor.committeeMember Marwaha, Aditi
dc.contributor.committeeMember Majid, Dewan
dc.contributor.committeeMember Lewis, Russell E.

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