L-arginine or tempol supplementation improves renal and cardiovascular function in rats with reduced renal mass and chronic high salt intake

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Carlström, MattiasKarolinska Institutet,Uppsala universitet,Institutionen för medicinsk cellbiologi (author)

L-arginine or tempol supplementation improves renal and cardiovascular function in rats with reduced renal mass and chronic high salt intake

Article/chapterEnglish2013

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2013-02-25
Wiley,2013
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LIBRIS-ID:oai:DiVA.org:uu-197953
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-197953URI
https://doi.org/10.1111/apha.12079DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:126313056URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Aim Early life reduction in nephron number and chronic high salt intake cause development of renal and cardiovascular disease, which has been associated with oxidative stress and nitric oxide (NO) deficiency. We investigated the hypothesis that interventions stimulating NO signalling or reducing oxidative stress may restore renal autoregulation, attenuate hypertension and reduce renal and cardiovascular injuries following reduction in renal mass and chronic high salt intake. Methods Male SpragueDawley rats were uninephrectomized (UNX) or sham-operated at 3weeks of age and given either a normal-salt (NS) or high-salt (HS) diet. Effects on renal and cardiovascular functions were assessed in rats supplemented with substrate for NO synthase (L-Arg) or a superoxide dismutase mimetic (Tempol). Results Rats with UNX+HS developed hypertension and displayed increased renal NADPH oxidase activity, elevated levels of oxidative stress markers in plasma and urine, and reduced cGMP in plasma. Histological analysis showed signs of cardiac and renal inflammation and fibrosis. These changes were linked with abnormal renal autoregulation, measured as a stronger tubuloglomerular feedback (TGF) response. Simultaneous treatment with L-Arg or Tempol restored cGMP levels in plasma and increased markers of NO signalling in the kidney. This was associated with normalized TGF responses, attenuated hypertension and reduced signs of histopathological changes in the kidney and in the heart. Conclusion Reduction in nephron number during early life followed by chronic HS intake is associated with oxidative stress, impaired renal autoregulation and development of hypertension. Treatment strategies that increase NO bioavailability, or reduce levels of reactive oxygen species, were proven beneficial in this model of renal and cardiovascular disease.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Urologi och njurmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Urology and Nephrology hsv//eng
hypertension
nephron number
oxidative stress

Added entries (persons, corporate bodies, meetings, titles ...)

Brown, Russell D.Uppsala universitet,Institutionen för medicinsk cellbiologi (author)
Yang, T.Karolinska Institutet (author)
Hezel, M.Karolinska Institutet (author)
Larsson, ErikUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)eriklars (author)
Scheffer, P. G. (author)
Teerlink, T. (author)
Lundberg, J. O.Karolinska Institutet (author)
Persson, A. Erik G.Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)erikpers (author)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

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In:Acta Physiologica: Wiley207:4, s. 732-7411748-17081748-1716

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

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