Human subjects with impaired baroreflex function cannot buffer rises or falls in blood pressure (BP), thus allowing BP effects of endogenous or environmental stimuli that previously escaped detection to emerge dramatically. Studies in these patients led us to discover that water ingestion induces a robust increase in BP and vascular resistance. This project explores the mechanism of waters cardiovascular effects using a mouse model of baroreflex impairment. We show that the pharynx, esophagus, and stomach are not critical sites for waters pressor action, and that plasma volume expansion does not contribute significantly to the rise in BP observed after water ingestion. We also show that the increase in BP after water ingestion is mediated through sympathetic nervous system activation, and appears to be independent of the effects of renin and angiontensin. Genetic knockout mouse models were used to investigate the potential role of several candidate molecular mediators. The osmosensitive transient receptor potential vanilloid 4 channel (TRPV4) was found to be an important component of the response. Although portal osmolality decreased after water ingestion in both wild-type and Trpv4-/- mice, only the wild-type animals showed a pressor response. The same volume of physiological saline failed to elicit an increase in BP, suggesting osmolality as the stimulus. The osmopressor response to water, and TRPV4 thus appear to be new factors now implicated in the physiology of BP regulation.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-09202011-205331 |
| Date | 19 October 2011 |
| Creators | McHugh, Julia |
| Contributors | Italo Biaggioni, David Robertson, Jens Jordan, John Oates, Kevin Strange |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-09202011-205331/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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