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Splenic neurohormonal modulation of renal and mesenteric hemodynamics in portal hypertension Open Access


Other title
portal hypertension
Type of item
Degree grantor
University of Alberta
Author or creator
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 of Physiology

Date accepted
Graduation date
Doctor of Philosophy
Degree level
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.
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