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Neural suppression of miRNA-181a in the kidney elevates renin expression and exacerbates hypertension in Schlager mice.
Jackson, Kristy L; Gueguen, Cindy; Lim, Kyungjoon; Eikelis, Nina; Stevenson, Emily R; Charchar, Fadi J; Lambert, Gavin W; Burke, Sandra L; Paterson, Madeleine R; Marques, Francine Z; Head, Geoffrey A.
Affiliation
  • Jackson KL; Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Gueguen C; Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Lim K; Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Eikelis N; Department of Physiology, Anatomy & Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, Australia.
  • Stevenson ER; Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Charchar FJ; Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, VIC, Australia.
  • Lambert GW; Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Burke SL; Faculty of Science and Technology, Federation University Australia, Ballarat, VIC, Australia.
  • Paterson MR; Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • Marques FZ; Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, VIC, Australia.
  • Head GA; Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Hypertens Res ; 43(11): 1152-1164, 2020 11.
Article de En | MEDLINE | ID: mdl-32427944
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.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Rénine / MicroARN / Hypertension artérielle / Rein Limites: Animals Langue: En Journal: Hypertens Res Sujet du journal: ANGIOLOGIA Année: 2020 Type de document: Article Pays d'affiliation: Australie

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Rénine / MicroARN / Hypertension artérielle / Rein Limites: Animals Langue: En Journal: Hypertens Res Sujet du journal: ANGIOLOGIA Année: 2020 Type de document: Article Pays d'affiliation: Australie
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