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Title page for ETD etd-07092014-111430

Type of Document Dissertation
Author Mai, Tu Hoang Anh
Author's Email Address tu.h.mai@vanderbilt.edu
URN etd-07092014-111430
Title Hypo-osmotic Effects in Cardiovascular Controls: Hepatic and Renal Mechanisms Underlying the Osmopressor Response
Degree PhD
Department Pharmacology
Advisory Committee
Advisor Name Title
Italo Biaggioni Committee Chair
David Harrison Committee Member
David Robertson Committee Member
John Oates Committee Member
Owen McGuinness Committee Member
  • osmolality
  • Osmopressor
  • water
  • autonomic nervous system
  • portal vein
  • renal nerve denervation
Date of Defense 2014-05-30
Availability unrestricted

Hypo-osmotic Effects in Cardiovascular Controls: Hepatic and Renal Mechanisms Underlying the Osmopressor Response.

Patients with baroreflex impairment experience a robust increase in blood pressure (BP) after 16 oz. of water consumption. This increase in BP was also significant in healthy elderly subjects though with smaller magnitude but absent in healthy young adults. Using the sino-aortic mouse model, the pressor response to water was replicated to a similar fashion as seen in humans. This response to water was named the “Osmopressor Response” (OPR) because osmolality played a significant role in the initiation and maintenance of BP elevation. One of the molecular mediators of this response was the transient receptor vanilloid potential (TRPV4). These channels were highly expressed in the nervous system, the gut, the liver and the kidneys. Hypotonicity was sensed in the liver to trigger the OPR, and the presence of TRPV4 in this region was required for the response to occur. One of the gastrointestinal nerves that innervates the liver is the splanchnic nerve that feeds into the celiac ganglion. Mice that underwent celiac ganglionectomy was still able to trigger the OPR, however, the duration of BP elevation was significantly less than in sham mice, indicating the important role of the celiac ganglia in the maintenance of the response. The renal nerves also play a crucial role in the OPR because mice that had bilateral renal nerve denervation had significantly diminished OPR compared to WT mice. Although the OPR was initially only observed in baroreflex-impaired patients and elderly, water ingestion and its effect on BP might be substantial. Water ingestion beyond thirst has been used therapeutically in conditions such as: the orthostatic hypotension of autonomic neuropathy, the orthostatic hypotension in multiple system atrophy (MSA); and possibly in postprandial angina pectoris. The American Red Cross now recommends drinking 16 oz. of water before blood donation to prevent syncope.


David Robertson, MD.

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