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J Physiol Volume 575, Number 3, 855-867, September 15, 2006 DOI: 10.1113/jphysiol.2006.111260
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RENAL AND ENDOCRINE

Prenatal exposure to interleukin-6 results in hypertension and alterations in the renin–angiotensin system of the rat

Anne-Maj Samuelsson1, Camilla Alexanderson1, Johan Mölne2, Börje Haraldsson3, Peter Hansell4 and Agneta Holmäng1

1 Cardiovascular Institute and Wallenberg Laboratory
2 Institute of Pathology
3 Department of Physiology and Nephrology, Göteborg University, Sahlgrenska Academy, Göteborg, Sweden
4 Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden

Cytokines are emerging as important in developmental processes. They may induce alterations in normal gene expression patterns, activate angiotensinogen transcription, or alter expression of the renin–angiotensin system (RAS). To determine whether prenatal exposure to interleukin-6 (IL-6) influences gene expression of the intrarenal RAS and contributes to renal dysfunction and hypertension in adulthood, we exposed female rats to IL-6 early (EIL-6 females) and late (LIL-6 females) in pregnancy and analysed blood pressure in the offspring at 5–20 weeks of age. Renal fluid and electrolyte excretion was assessed in clearance experiments, mRNA expression by real-time PCR, and protein levels by Western blot. Systolic pressure was increased at 5 weeks in IL-6 females and at 11 weeks in males. Circulatory RAS levels were increased in all IL-6 females, but angiotensin-1-converting enzyme (ACE) activity was increased only in LIL-6 females. LIL-6 males and IL-6 females showed decreased urinary flow rate and urinary sodium and potassium excretion. Dopamine excretion was decreased IL-6 females. In adult renal cortex, renin expression was increased in all IL-6 females, but angiotensinogen mRNA was increased only in LIL-6 females; AT1 receptor (AT1-R) mRNA and protein levels were increased in LIL-6 females, whereas AT2 receptor (AT2-R) levels were decreased in LIL-6 females and EIL-6 males. In adult renal medulla, AT1-R protein levels were increased in LIL-6 females, and AT2-R mRNA and protein levels were decreased in EIL-6 males and LIL-6 females. Prenatal IL-6 exposure may cause hypertension by altering the renal and circulatory RAS and renal fluid and electrolyte excretion, especially in females.

(Received 10 April 2006; accepted after revision 30 June 2006; first published online 6 July 2006)
Corresponding author A.-M. Samuelsson: Institute of Neuroscience and Physiology, Göteborg University, S-413 45 Göteborg, Sweden. Email: anne-maj.samuelsson{at}wlab.gu.se







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