In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
Abstract:
Emerging evidence suggests an interaction between renal inflammation and afferent renal nerves in some preclinical models of hypertension. In this study we tested the hypothesis that the inflammatory cytokine IL-1β interacts with afferent renal nerves in the pathogenesis of the DOCA-salt mouse model of hypertension. Specifically, we compared the effect of total renal denervation (TRDN) and afferent RDN (ARDN) on the development of DOCA-salt hypertension to that observed in animals receiving the IL-1 receptor antagonist anakinra. In the first study , 10-week-old male C57BL6/J mice were implanted with radiotelemeters for measurement of mean arterial pressure (MAP). DOCA was administered via subcutaneous pellet containing 50 mg of DOCA, controls received a drug free pellet. Uni-nephrectomy, pellet insertion, salt treatment, TRDN, ARDN, or sham denervation were all performed on the same day. TRDN and ARDN was performed through peri-axonal application of phenol and capsaicin respectively. In the second study , the IL-1 receptor antagonist anakinra (75mg/kg) or vehicle control (0.9% saline) was delivered via intraperitoneal injection daily 10 days post-induction of hypertension. Renal cytokine protein was quantified by Multiplex ELISA. All values reported are mean + SEM, all groups n=5. In the first study , MAP increased in sham treated DOCA-salt mice +43 ± 1 mmHg from baseline by the end of the 3 rd week of DOCA-salt. This response was attenuated by 40% in TRDN (+26 ± 4 mmHg) and by 44% in ARDN DOCA-salt mice (+24 ± 3 mmHg). IL-1β was increased in DOCA-salt kidneys (2.1 ± 0.4 pg/mg) compared to control kidneys (0.36 ± 0.1 pg/mg). In the second study , anakinra similarly attenuated the increase in MAP by 45% (+21 ± 2 mmHg) compared to vehicle controls (+38 ± 1 mmHg). Neither ARDN nor IL-1 receptor antagonism had any effect on renal inflammatory cytokines IL-1β, IL-6, or TNFα. The comparable attenuation in the MAP response to DOCA-salt ARDN and anakinra treated groups as well as the unchanged inflammatory phenotype is consistent with a common mechanism of action. We hypothesize that intrarenal IL-1β activates sympathoexcitatory renal afferent nerves to increase MAP in DOCA-salt mice. Future studies are needed to directly test this hypothesis.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.79.suppl_1.032
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2094210-2
