title: Prenatal exposure to lipopolysaccharide alters the intrarenal renin-angiotensin system and renal damage in offspring rats.
abstract: Prenatal exposure to inflammation produces offspring that are hypertensive in adulthood. This study explored alterations of the renin-angiotensin system (RAS) during the development of hypertension induced by prenatal exposure to lipopolysaccharide (LPS). In addition, the effects of an inhibitor of the nuclear transcription factor (NF)-kappaB (pyrrolidine dithiocarbamate, PDTC) on this process were assessed. Pregnant rats were randomly divided into four groups (n=8): a control group, an LPS group, a PDTC group and an LPS+PDTC group. The rats in these groups were intraperitoneally administered vehicle, 0.79 mg kg(-1) LPS, 100 mg kg(-1) PDTC or LPS plus PDTC, respectively. LPS was given on the 8th, 10th and 12th days, whereas PDTC was given from the 8th to the 14th day during gestation. At various ages from day 1 to 25 weeks, plasma renin activity, plasma angiotensin II (Ang II) levels, renal function, glomerular number, mRNA expression levels of renal cortex renin and angiotensin-converting enzyme (ACE), the number of Ang II-positive cells and NF-kappaB activation were determined. The results showed that prenatal exposure to LPS resulted in significantly lower glomerular numbers and creatinine clearance rates and higher urinary protein and renal cortex ACE mRNA expression in adult offspring. Prenatal LPS also decreased the renal cortex renin mRNA expression and the number of Ang II-positive cells in offspring at 1 day of age, but these increased at 7, 16 and 25 weeks, whereas the plasma renin activity and Ang II concentration remained unchanged. Simultaneously, PDTC treatment markedly reversed the action of LPS. In conclusion, prenatal exposure to LPS resulted in alteration of the intrarenal RAS and renal damage in adult offspring rats.
authors.affiliation: Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Hao
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Zhang
authors.forename: Zhi-Bing
authors.initials: ZB
authors.lastname: Yuan
authors.forename: Dan-Li
authors.initials: DL
authors.lastname: Yang
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Hao
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D016328:NF-kappa B / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011507:Proteinuria / Q000139:chemically induced; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000096:biosynthesis / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D000804:Angiotensin II; C020972:pyrrolidine dithiocarbamic acid; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D003401:Creatine