Interaction Of Afferent Renal Nerve Activity And Il-1R Signaling In Hypertension
2024-04
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Interaction Of Afferent Renal Nerve Activity And Il-1R Signaling In Hypertension
Authors
Published Date
2024-04
Publisher
Type
Thesis or Dissertation
Abstract
Renal denervation was recently approved by the FDA for the treatment of hypertension, but the mechanism by which it reduces blood pressure is unclear. Studies of patients who have received the treatment have shown a variety of off-target improvements in conditions associated with sympathetic overactivity. One explanation is that these effects are due to ablation of sympathoexcitatory afferent renal nerves, which are overactive under conditions of renal inflammation. Renal interleukin 1-beta (IL-1β) is elevated in many cases of hypertension, as well as the DOCA-salt model of hypertension, and its activity may be responsible for the elevation in afferent renal nerve activity and arterial pressure. IL-1R activation increases the activity of afferent sensory nerves in other contexts. In these studies, I sought to determine if IL-1R activity was responsible for the increased afferent renal nerve activity characteristic of DOCA-salt hypertension. First, I characterized a mouse model of DOCA-salt hypertension and found that ablation of the afferent renal nerves attenuates hypertension in this model. Next, I used this model in combination with two methods of IL-1R disruption: genetic IL-1R knockout and pharmacological IL-1R antagonism. These methods attenuated hypertension in this model system. Further, combining either method with afferent renal denervation produced no additional attenuation of hypertension, and an acute depressor response to delivery of the IL-1R antagonist was observed only in animals with intact renal afferent nerves, indicating a common mechanism of action. In combination, these findings suggest that IL-1R activation is partially responsible for the elevated afferent renal nerve activity which stimulates central sympathetic outflow to renal and non-renal targets to drive DOCA-salt hypertension.
Description
University of Minnesota Ph.D. dissertation. April 2024. Major: Integrative Biology and Physiology. Advisor: John Osborn. 1 computer file (PDF); vi, 114 pages.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.