Premium
Prenatal exposure to interleukin‐6 results in hypertension and alterations in the renin–angiotensin system of the rat
Author(s) -
Samuelsson AnneMaj,
Alexanderson Camilla,
Mölne Johan,
Haraldsson Börje,
Hansell Peter,
Holmäng Agneta
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.111260
Subject(s) - endocrinology , medicine , renin–angiotensin system , offspring , blood pressure , excretion , kidney , plasma renin activity , receptor , urinary system , biology , pregnancy , genetics
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; AT 1 receptor (AT 1 ‐R) mRNA and protein levels were increased in LIL‐6 females, whereas AT 2 receptor (AT 2 ‐R) levels were decreased in LIL‐6 females and EIL‐6 males. In adult renal medulla, AT 1 ‐R protein levels were increased in LIL‐6 females, and AT 2 ‐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.