RESUMEN
OBJECTIVE: To explore the impact of prenatal exposure to lipopolysaccharide on renin-angiotensin system of offspring rats. METHODS: Six pregnant SD rats were randomly divided into 2 groups. The rats in the lipopolysaccharide (LPS) group were treated with LPS 0.79 mg/kg (i.p.) on the 8th, 10th and 12th day of gestation, and rats in the control group were treated with saline at the same time points. The blood pressure of offspring rats was measured by the tail cuff method. Protein expression of Angiotensin II (AngII) in thoracic aorta vessel was determined by immunohistochemistry. Protein expressions of AngII type 1 and type 2 receptor in thoracic aorta vessel were detected by Western blot. RESULTS: Blood pressure of 12-week-old offspring rats of LPS group was significantly higher than that of 12-week-old offspring rats of control group (P < 0.01). The protein expression of AngII and AngII type 1 receptor in thoracic aorta vessel were significantly higher while protein expression of AngII type 2 receptor was lower in 15-week-old offspring rats of LPS group than in control group, resulting in a significant increase in the ratio of AngII type 1 receptor/AngII type 2 receptor in the aorta at 15-week-old of offspring rats than in 15-week-old offspring rats of control group (P < 0.01). CONCLUSION: Prenatal lipopolysaccharide exposure results vascular renin-angiotensin system dysfunction, which may play an important role on the pathogenesis of hypertension development in offspring rats.
Asunto(s)
Hipertensión/etiología , Lipopolisacáridos/efectos adversos , Exposición Materna/efectos adversos , Sistema Renina-Angiotensina/efectos de los fármacos , Angiotensina II/metabolismo , Animales , Animales Recién Nacidos , Presión Sanguínea , Femenino , Hipertensión/metabolismo , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
Prenatal exposure to inflammation produces offspring that are hypertensive in adulthood. The present study was to explore the role of intrarenal renin-angiotensin (Ang) system in the development of hypertension programmed by prenatal exposure to zymosan. Pregnant rats were randomly divided into control group and zymosan group (n = 6). Rats in these two groups were administered intraperitoneally with 0.5 ml vehicle and 2.37 mg/kg zymosan, respectively, on the eighth, tenth, and 12th day during gestation. The results showed the glomerular number and creatinine clearance rate decreased significantly in offspring of zymosan-treated rats. The renal cortex renin mRNA expression, Ang II-positive cells in renal cortex, and Ang II expression in renal medulla increased significantly in offspring of zymosan-treated rats at 7, 16, and 25 weeks of age. The plasma renin activity and Ang II concentration were unchanged. In conclusion, prenatal exposure to zymosan resulted in the activation of intrarenal renin-Ang system in adult offspring rats.
Asunto(s)
Hipertensión/fisiopatología , Inflamación/fisiopatología , Glomérulos Renales/fisiopatología , Efectos Tardíos de la Exposición Prenatal , Sistema Renina-Angiotensina/fisiología , Angiotensina II/sangre , Angiotensina II/genética , Animales , Presión Sanguínea , Creatinina/metabolismo , Femenino , Expresión Génica , Hipertensión/sangre , Hipertensión/metabolismo , Inflamación/patología , Pruebas de Función Renal , Glomérulos Renales/patología , Reacción en Cadena de la Polimerasa , Embarazo , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Renina/sangre , Renina/genética , Renina/metabolismo , Zimosan/inmunologíaRESUMEN
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.
