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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Angiotensinogen

biosynthesis

genetics

Animals

Blood Pressure

drug effects

Dopamine

urine

Female

Gene Expression Regulation

Hypertension

blood

chemically induced

physiopathology

Interleukin-6

toxicity

Kidney

drug effects

metabolism

Male

Peptidyl-Dipeptidase A

blood

Pregnancy

Prenatal Exposure Delayed Effects

RNA

Messenger

biosynthesis

Rats

Rats

Wistar

Receptor

Angiotensin

Type 1

biosynthesis

genetics

Renin

biosynthesis

blood

genetics

Renin-Angiotensin System

Sex Factors

Sodium

urine

Time Factors

Urodynamics

drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)