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Genetic Abrogation ...
Genetic Abrogation of Adenosine A(3) Receptor Prevents Uninephrectomy and High Salt-Induced Hypertension
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- Yang, Ting (author)
- 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.
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- Zollbrecht, Christa (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden.
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- Winerdal, Malin E. (author)
- Karolinska Institutet
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- Zhuge, Zhengbing (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden.
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- Zhang, Xing-Mei (author)
- Karolinska Institutet
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- Terrando, Niccolo (author)
- 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.;Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA.
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- Checa, Antonio (author)
- Karolinska Institutet
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- Sällström, Johan (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden.
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- Wheelock, Craig E. (author)
- Karolinska Institutet
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- Winqvist, Ola (author)
- Karolinska Institutet
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- Harris, Robert A. (author)
- Karolinska Institutet
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- Larsson, Erik (author)
- Uppsala universitet,Klinisk och experimentell patologi
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- Persson, A. Erik G. (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Fredholm, Bertil B. (author)
- Karolinska Institutet
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- Carlström, Mattias (author)
- Karolinska Institutet
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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. (creator_code:org_t)
- 2016
- 2016
- English.
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In: Journal of the American Heart Association. - 2047-9980. ; 5:7
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- adenosine receptor
- cardiovascular disease
- high salt diet
- inflammation
- kidney
- nephron number
- NADPH oxidase
- uninephrectomy
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Yang, Ting
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Zollbrecht, Chri ...
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Winerdal, Malin ...
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Zhuge, Zhengbing
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Zhang, Xing-Mei
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Terrando, Niccol ...
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Checa, Antonio
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Sällström, Johan
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Wheelock, Craig ...
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Winqvist, Ola
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Harris, Robert A ...
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Larsson, Erik
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Persson, A. Erik ...
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Fredholm, Bertil ...
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Carlström, Matti ...
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Uppsala University
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Karolinska Institutet