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Renal sensory nerves increase sympathetic nerve activity and blood pressure in 2-Kidney 1-Clip hypertensive mice

Ong, Jason (2020) Renal sensory nerves increase sympathetic nerve activity and blood pressure in 2-Kidney 1-Clip hypertensive mice. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Renal denervation lowers arterial blood pressure (ABP) in multiple clinical trials and some experimental models of hypertension. These antihypertensive effects have been attributed to the removal of renal afferent nerves. The purpose of the present study was to define the function, anatomy, and contribution of mouse renal sensory neurons to a renal-nerve dependent model of hypertension. First, electrical stimulation of mouse renal afferent nerves produced frequency-dependent increases in ABP that were eliminated by ganglionic blockade. Stimulus-triggered averaging revealed renal afferent stimulation significantly increased splanchnic, renal, and lumbar sympathetic nerve activity (SNA). Second, kidney injection of wheat germ agglutinin into male C57Bl6 mice (12-14 weeks, Jackson Laboratories) produced ipsilateral labeling in the T11-L2 dorsal root ganglia. Next, 2K1C hypertension was produced in male C57Bl6 mice (12-14 weeks, Jackson Laboratories) by placement of a 0.5mm length of PTFE tubing around the left renal artery. 2K1C mice displayed an elevated ABP measured via telemetry and greater fall in mean ABP to ganglionic blockade at day 14 or 21 vs day 0. Renal afferent discharge was significantly higher in 2K1C-clipped versus 2K1C-unclipped or sham kidneys. In addition, 2K1C-clipped versus 2K1C-unclipped or sham kidneys had lower renal mass and higher mRNA levels of several pro-inflammatory cytokines. Finally, both ipsilateral renal denervation (10% phenol) or selective denervation of renal afferent nerves (periaxonal application of 33 mM capsaicin) at time of clipping resulted in lower ABP of 2K1C mice at Days 14 or 21. These findings suggest mouse renal sensory neurons are activated to increase SNA and ABP in 2K1C hypertension.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Ong, Jasonjao60@pitt.edujao60
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairStocker,
Committee MemberSesack,
Committee MemberSved,
Committee MemberFink,
Date: 1 May 2020
Date Type: Publication
Defense Date: 13 February 2020
Approval Date: 1 May 2020
Submission Date: 3 March 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 43
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
David C. Frederick Honors College
Degree: BPhil - Bachelor of Philosophy
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: autonomic, blood pressure, hypertension, sensory, sympathetic
Date Deposited: 01 May 2020 18:49
Last Modified: 01 May 2020 18:49


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