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renal, portal hypertension, spleen

Hamza, Shereen M.

Supervisor and department: Jacobs, Susan Physiology

Examining committee member and department: Benishin, Christina Physiology Smith, Peter A. Pharmacology Braam, Branko Physiology Kassiri, Zamaneh Physiology Lee, Samuel S. Medicine; University of Calgary

Department: Department of Physiology

Specialization:

Date accepted: 2009-08-05T20:14:12Z

Graduation date: 2009-11

Degree: Doctor of Philosophy

Degree level: Doctoral

Abstract: Persistent elevation of portal venous pressure portal hypertension- PH, is linked to chronic liver disease and invariably leads to multi-organ circulatory complications. Hallmarks of PH are renal dysfunction and a characteristic hemodynamic profile hyperdynamic circulation, which synergistically cause the development of the fatal sequelae of PH. Despite extensive research, PH remains a serious clinical problem, with no effective treatment. In large part, this is due to lack of comprehensive knowledge regarding the initiation and early progression of renal dysfunction and the hyperdynamic circulation. The spleen, which is actively engaged in cardiovascular regulation, is intimately connected with the portal venous system such that splenic venous pressure SVP is also elevated in PH. We therefore investigated the contribution of the spleen to PH-related cardiovascular dysregulation. Specifically, we employed an acute rat model to elucidate the existence of neurohormonal pathways activated in early PH. It was known that PH-related renal dysfunction is functional and neurally mediated via the hepato-renal reflex. We hypothesized that, in addition, selective elevation of splenic venous pressure SVP also increases renal vascular resistance and modulates renal vascular function, through reflex activation of splenic afferent and renal sympathetic nerves. Indeed, acutely elevated SVP by partial splenic vein occlusion SVO did increase splenic afferent nerve activity and reflexly increased renal sympathetic nerve activity RSNA. Simultaneously, renal blood flow RBF and renal arterial conductance fell; this was α1 adrenergic receptor-mediated and dependent on intact splenic and renal nerves. Moreover, our data showed that, in the absence of increased SVP, PH did not affect RSNA or renal vascular function. Although splanchnic vasodilation is characteristic of the hyperdynamic circulation in PH, its development is thought to be contingent upon an initial transient mesenteric vasoconstriction. Our data revealed that increased SVP reflexly activates mesenteric efferent nerves, and reduces mesenteric arterial blood flow, vascular conductance and resistance artery diameter; this was primarily mediated through angiotensin II release spleno-renal reflex-, renal baroreceptor-, and mesenteric angiotensinergic nerve-mediated. In conclusion, the spleen neurohormonally modulates renal and mesenteric circulations, thus contributing to the initiation of renal dysfunction and hyperdynamic circulation of PH.

Language: English

DOI: doi:10.7939-R3KP7P

Rights: Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.





Autor: Hamza, Shereen M.

Fuente: https://era.library.ualberta.ca/



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