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Inhibition of TLR4 Activation Prevents Renal Autoregulatory Impairment in Ang II Hypertensive Rats
Author(s) -
Freeman Brian,
Zhang Shali,
Cook Anthony,
Inscho Edward W.
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.569.1
Subject(s) - afferent arterioles , arteriole , medicine , angiotensin ii , endocrinology , renal function , blood pressure , tlr4 , chemistry , kidney , autoregulation , receptor , microcirculation
Autoregulation by afferent arterioles regulates renal blood flow and glomerular filtration rate across widely ranging arterial pressures. Autoregulatory function is impaired in hypertension, perhaps due to release of damage associated molecular patterns that activate renal toll‐like receptor (TLR4). Autoregulatory impairment can promote hypertensive kidney injury. We hypothesize that inhibition of TLR4 activation preserves afferent arteriole autoregulatory function in Angiotensin II (AngII) hypertension. Three groups (n=4/group) of male Sprague‐Dawley rats were implanted with osmotic minipumps set to deliver: saline (0.9% NaCl) or AngII (60ng/min). Group three received AngII+anti‐TLR4 Ab (3 μg/ml/kg/day, i.p.) for 14 days. Systolic blood pressure (SBP) was assessed (days 0, 3, 7 and 13). Kidneys were harvested on day 14 for juxtamedullary nephron assessment of afferent arteriole autoregulatory function. SBP increased in the AngII and AngII+Anti‐TLR4 Ab groups compared to saline controls over the 14 days (P<0.05), averaging 198 ± 11, 200 ± 8 and 135 ± 3 mmHg, respectively. Baseline arteriole diameters (100 mmHg) averaged 14 ± 0.8, 15.6 ± 1.7, and 13 ± 0.3 microns for control, AngII and AngII+Anti‐TLR4 Ab, respectively. Perfusion pressure was decreased to 65 mmHg and increased to 170 mmHg in 15 mmHg increments. At 170 mmHg, arteriole diameters decreased by 31 ± 6% and 33 ± 8% of baseline in the control and Ang II+Anti‐TLR4 Ab groups whereas the AngII group had a decline of 11.7 ± 3.7%. These data establish that autoregulatory function is Impaired in AngII hypertensive rats while it is preserved by anti‐TLR4 Ab‐treatment. These findings implicate chronic TLR4 activation as causative in the hypertensive decline in autoregulatory capability. Support or Funding Information Funded by NHLBI; 1R25 HL115473‐01 and DK044628‐20. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .