[Prenatal exposure to lipolysaccharide result in expression changes of myocardial renin angiotensin system in offspring rats]

Abstract

Objective: To explore expression changes of myocardial renin angiotensin system induced by prenatal exposure to lipopolysaccharide in offspring rats.

Methods: Twelve pregnant SD rats were randomly divided into three groups: LPS model group: intraperitoneal injection of LPS (0.79 mg/kg) at 8, 10, 12 days of pregnancy; control group: intraperitoneal injection of sterile saline (0.5 ml) at 8, 10, 12 days of pregnancy; LPS + PDTC group: intraperitoneal injection of LPS (0.79 mg/kg) at 8, 10, 12 days of pregnancy plus daily intraperitoneal injection of NF-κB inhibitor -pyrrolidine dithiocarbamate (PDTC, 100 mg/kg) on day 8 to 14 pregnancy day. Protein expression of AngiotensinII(AngII) in heart was detected by immunohistochemistry; myocardial ACE,ACE2 mRNA expression was detected by real-time PCR; protein expression of ACE and ACE2 in heart was detected by Western blot in offspring rats of various groups.

Results: Compared with control group (0.07 ± 0.02,0.11 ± 0.01), AngII protein levels (0.14 ± 0.04) were significantly increased at 6 weeks (P < 0.01) and 16 weeks (0.17 ± 0.04, P < 0.05) in offspring rats of LPS model group, which could be significantly attenuated by PDTC intervention (0.10 ± 0.01,0.13 ± 0.03, respectively, all P < 0.05).Similarly, myocardial ACE mRNA expression in 16 weeks offspring rats of LPS model group was significantly upregulated compared with control group (1.10 ± 0.26 vs.0.72 ± 0.22, P < 0.05), which was significantly attenuated by PDTC intervention (0.67 ± 0.01, P < 0.01 vs.LPS group). Myocardial protein expression ACE2 in 16 weeks offspring rats of LPS model group was significantly downregulated compared to control group, which was slightly upregulated by PDTC intervention (P > 0.05).

Conclusion: Pregnancy exposure to lipopolysaccharide increases myocardial ACE and AngII expression while reduces myocardial ACE2 expression in offspring rats, which might be one of the pathomechanisms of offspring hypertension.