uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genetic Abrogation of Adenosine A(3) Receptor Prevents Uninephrectomy and High Salt-Induced Hypertension
Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden.;Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA..
Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden..
Karolinska Inst, Dept Med, Unit Translat Immunol, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden..
Show others and affiliations
2016 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 7, article id e003868Article in journal (Refereed) Published
Abstract [en]

Background - Early-life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the specific role of the A(3) receptor in cardiovascular diseases is not clear. In this study, gene-modified mice were used to investigate the hypothesis that lack of A(3) signaling prevents the development of hypertension and attenuates renal and cardiovascular injuries following UNX in combination with HS (UNX-HS) in mice.

Methods and Results - Wild-type (A(3)(+/+)) mice subjected to UNX-HS developed hypertension compared with controls (mean arterial pressure 106 +/- 3 versus 82 +/- 3 mm Hg; P<0.05) and displayed an impaired metabolic phenotype (eg, increased adiposity, reduced glucose tolerance, hyperinsulinemia). These changes were associated with both cardiac hypertrophy and fibrosis together with renal injuries and proteinuria. All of these pathological hallmarks were significantly attenuated in the A(3)(-/-) mice. Mechanistically, absence of A(3) receptors protected from UNX-HS-associated increase in renal NADPH oxidase activity and Nox2 expression. In addition, circulating cytokines including interleukins 1 beta, 6, 12, and 10 were increased in A(3)(+/+) following UNX-HS, but these cytokines were already elevated in naive A(3)(-/-) mice and did not change following UNX-HS.

Conclusions - Reduction in nephron number combined with chronic HS intake is associated with oxidative stress, chronic inflammation, and development of hypertension in mice. Absence of adenosine A(3) receptor signaling was strongly protective in this novel mouse model of renal and cardiovascular disease.

Place, publisher, year, edition, pages
2016. Vol. 5, no 7, article id e003868
Keyword [en]
adenosine receptor, cardiovascular disease, high salt diet, inflammation, kidney, nephron number, NADPH oxidase, uninephrectomy
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-308953DOI: 10.1161/JAHA.116.003868ISI: 000386713800063OAI: oai:DiVA.org:uu-308953DiVA: diva2:1052847
Funder
Swedish Research Council, 521-2011-2639, K2009-64X-03522Swedish Heart Lung Foundation, 20110589, 20140448Swedish Society for Medical Research (SSMF)
Available from: 2016-12-07 Created: 2016-12-01 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Search in DiVA

By author/editor
Larsson, ErikPersson, A. Erik G.
By organisation
Clinical and experimental pathologyDepartment of Medical Cell Biology
In the same journal
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 475 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf