- Title
- Neural suppression of miRNA-181a in the kidney elevates renin expression and exacerbates hypertension in Schlager mice
- Creator
- Jackson, Kristy; Gueguen, Cindy; Lim, Kyungjoon; Eikelis, Nina; Stevenson, Emily; Charchar, Fadi; Lambert, Gavin; Burke, Sandra; Paterson, Madeleine; Marques, Francine; Head, Geoffrey
- Date
- 2020
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/174497
- Identifier
- vital:14837
- Identifier
-
https://doi.org/10.1038/s41440-020-0453-x
- Identifier
- ISBN:0916-9636 (ISSN)
- Abstract
- BPH/2J mice are a genetic model of hypertension with overactivity of the sympathetic nervous system (SNS) and renin–angiotensin system (RAS). BPH/2J display higher renal renin mRNA and low levels of its negative regulator microRNA-181a (miR-181a). We hypothesise that high renal SNS activity may reduce miR-181a expression, which contributes to elevated RAS activity and hypertension in BPH/2J. Our aim was to determine whether in vivo administration of a renal-specific miR-181a mimic or whether renal denervation could increase renal miR-181a abundance to reduce renal renin mRNA, RAS activity and hypertension in BPH/2J mice. Blood pressure (BP) in BPH/2J and normotensive BPN/3J mice was measured via radiotelemetry probes. Mice were administered miR-181a mimic or a negative control (1–25 nmol, i.v., n = 6–10) with BP measured for 48 h after each dose or they underwent renal denervation or sham surgery (n = 7–9). Injection of 5–25 nmol miR-181a mimic reduced BP in BPH/2J mice after 36–48 h (−5.3 ± 1.8, −6.1 ± 1.9 mmHg, respectively, P < 0.016). Treatment resulted in lower renal renin and inflammatory marker (TLR4) mRNA levels in BPH/2J. The mimic abolished the hypotensive effect of blocking the RAS with enalaprilat (P < 0.01). No differences between mimic or vehicle were observed in BPN/3J mice except for a higher level of renal angiotensinogen in the mimic-treated mice. Renal miR-181a levels that were lower in sham BPH/2J mice were greater following renal denervation and were thus similar to those of BPN/3J. Our findings suggest that the reduced renal miR-181a may partially contribute to the elevated BP in BPH/2J mice, through an interaction between the renal sympathetic nerves and miR-181a regulation of the RAS. © 2020, The Japanese Society of Hypertension.; This work was supported by a grant from the National Health & Medical Research Council of Australia (NHMRC, Project grant 1065714) and in part by the Victorian Government’s OIS Program. Investigators were supported by NHMRC/National Heart Foundation (NHF) Postdoctoral Fellowships (NHMRC APP1091688 to KLJ, NHMRC APP1052659 and NHF PF12M6785 and 101185 to FZM) and NHMRC Research Fellowships (APP1042492 to GWL and APP1002186 to GAH).
- Publisher
- Springer Nature
- Relation
- Hypertension Research Vol. 43, no. 11 (2020), p. 1152-1164
- Rights
- Metadata is freely available under a CCO license
- Rights
- Copyright © 2020 Springer Nature Limited
- Subject
- 1102 Cardiorespiratory Medicine and Haematology; 1103 Clinical Sciences; Hypertension; MicroRNA; Renal denervation; Renin–angiotensin system; Sympathetic
- Reviewed
- Funder
- This work was supported by a grant from the National Health & Medical Research Council of Australia (NHMRC, Project grant 1065714) and in part by the Victorian Government’s OIS Program. Investigators were supported by NHMRC/National Heart Foundation (NHF) Postdoctoral Fellowships (NHMRC APP1091688 to KLJ, NHMRC APP1052659 and NHF PF12M6785 and 101185 to FZM) and NHMRC Research Fellowships (APP1042492 to GWL and APP1002186 to GAH).
- Hits: 6422
- Visitors: 6123
- Downloads: 0