title: Prenatal exposure to interleukin-6 results in hypertension and alterations in the renin-angiotensin system of the rat.
abstract: 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.
authors.affiliation: Institute of Neuroscience and Physiology, Göteborg University, S-413 45 Göteborg, Sweden. anne-maj.samuelsson@wlab.gu.se
authors.forename: Anne-Maj
authors.initials: AM
authors.lastname: Samuelsson
authors.forename: Camilla
authors.initials: C
authors.lastname: Alexanderson
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.forename: Börje
authors.initials: B
authors.lastname: Haraldsson
authors.forename: Peter
authors.initials: P
authors.lastname: Hansell
authors.forename: Agneta
authors.initials: A
authors.lastname: Holmäng
mesh_terms: D000808:Angiotensinogen / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000652:urine; D005260:Female; D005786:Gene Expression Regulation; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D015850:Interleukin-6 / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics; D012083:Renin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System; D012737:Sex Factors; D012964:Sodium / Q000652:urine; D013997:Time Factors; D014563:Urodynamics / Q000187:drug effects
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D004298:Dopamine