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Renal Sensory Nerves Increase Blood Pressure and Sympathetic Nerve Activity in 2‐Kidney 1‐Clip Hypertensive Mice
Author(s) -
Ong Jason,
Sved Alan F,
Kinsman Brian J.,
Tan Roderick J,
Rush Brittney M,
Carrattino Marcelo D,
Stocker Sean D
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.565.2
Subject(s) - blood pressure , medicine , renal artery , kidney , denervation , afferent , stimulation , hexamethonium , endocrinology
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 determine whether renal sensory nerves contribute to the 2‐Kidney‐1‐Clip (2K1C) model of hypertension. 2K1C hypertension was produced in male C57B16 mice (12–14 weeks, Jackson Laboratories) by placement of a 0.5mm length of PTFE tubing (ID: 0.008” x OD: 0.014”) around the left renal artery. 2K1C mice (n=10) displayed an elevated ABP measured via telemetry (Day 0: 96 ± 1mmHg vs Day 14: 120 ± 3mmHg; P<0.01). Ganglionic blockade with hexamethonium (30mg/kg, ip) produced a greater fall in mean ABP at Day 14 vs Day 0 (Day 0: −35 ± 2mmHg vs Day 14: −57 ± 5mmHg; P<0.01). 2K1C‐clipped kidneys vs 2K1C‐unclipped kidneys had lower mass (105 ± 14mg vs 173 ± 8mg, respectively; P<0.05) and higher mRNA levels of several pro‐inflammatory cytokines (IL1B, IL2, IL10, TNFa; P<0.05). Renal afferent discharge was significantly higher in 2K1C‐clipped kidneys vs 2K1C‐unclipped vs sham mice (2K1C‐clipped: 3.4 ± 0.9 Hz vs 2K1C‐unclipped: 0.7 ± 0.3Hz vs control: 0.3 ± 0.1 Hz, n=6/group; P<0.05). Furthermore, electrical stimulation of renal afferent nerves in control mice (n=6) produced a frequency‐dependent increase in ABP (5Hz: 4 ± 1mmHg, 10Hz: 6 ± 1mmHg, 20Hz: 11 ± 2mmHg; P<0.05). These responses were eliminated after ganglionic blockade with 5mg/kg chlorisondamine (5Hz: 1 ± 1mmHg, 10Hz: 1 ± 1mmHg, 20Hz: 1 ± 1mmHg, n=4/group; P<0.05). Stimulus‐triggered averaging of SNA during stimulation of renal afferent nerves (1 Hz, 200uA) revealed significant (P<0.05, n=4/group) increases in splanchnic (179 ± 11%), renal (195 ± 15%), and lumbar (167 ± 9%) SNA. Interestingly, the latency to the peak SNA (142 ± 10ms) suggests supraspinal pathways mediate the sympathoexcitatory response. Finally, both total renal denervation (10% phenol) or selective denervation of renal afferent nerves (periaxonal application of 33mM capsaicin) at time of clipping resulted in lower ABP than 2K1C mice at Day 14 (2K1C: 120 ± 3mmHg, phenol: 106 ± 3mmHg, capsaicin: 108 ± 3mmHg, n=6–10/group; P<0.05). These findings suggest 2K1C hypertension depends on renal sensory nerves and elevated SNA via supraspinal pathways. Support or Funding Information NIH grant HL113270, AHA Undergraduate Research Fellowship This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .