Document Type

Dissertation

Date of Degree

Spring 2015

Degree Name

PhD (Doctor of Philosophy)

Degree In

Pharmacology

First Advisor

Curt D. Sigmund

Abstract

Fluid balance is critical for cells to maintain at homeostasis as disturbances in it can disrupt cellular function and consequently the physiology of an organism. Fluid loss for an organism can be classified as either intra- or extracellular, and it appears that different mechanisms have developed to restore homeostasis after intra- or extracellular dehydration. The renin-angiotensin system (RAS) has been shown to be an important mediator of extracellular dehydration induced fluid intake. Various lines of evidence have demonstrated the importance of the subfornical organ (SFO) to mediate fluid intake, especially due to the RAS, and we have shown that production and action of angiotensin (ANG) at the SFO is necessary for fluid intake due to ANG within the brain. Protein kinase C (PKC), specifically PKC-a;, is shown to be a necessary and sufficienty sufficient effector in the SFO to mediate brain angiotensin-II (ANG-II) polydipsia. It is also demonstrated that production of ANG from the SFO is sufficient to increase fluid intake through the ANG-II type 1 (AT1R) receptor and PKC. While production of ANG from the SFO is sufficient to increase fluid intake it is not sufficient to increase blood pressure, metabolism, or sodium appetite. Thus, production and action of ANG to activate PKC-a; is both necessary and sufficient to increase fluid intake at the SFO, and the fluid, pressor, and metabolic phenotypes of brain ANG through the SFO can be separated.

Keywords

Fluid balance, Renin angiotensin system, Subfornical organ

Pages

xiv, 170

Bibliography

153-170

Comments

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Copyright

Copyright 2015 Jeffrey Coble

Included in

Pharmacology Commons

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