Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC291
Effects of prenatal hypoxia-ischemic in the motor behavior and cardiovascular system
I. M. Sab1, M. Ferraz1, M. Moss1, M. Ferraz1, A. Resende1, T. Brunini1, A. Mendes-Ribeiro1,2
1. Farmacologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. 2. Disciplina de Farmacologia, Departamento de Ci
Prenatal hypoxia-ischemia (HI) is one of the major causes of mortality and chronic neurological diseases in newborns that can evoke permanent effects such as mental retardation, learning difficulty, epilepsy and cerebral palsy (1). Moreover, changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases. However, the exact mechanisms underlying this relationship remain unknown. Nitric oxide (NO) is a lipophylic gas which has many physiological functions, including vasodilatation, neurotransmission and platelet function inhibition. NO bioavailability depends on both its synthesis and its degradation by oxidative stress (2). The aim of our study is to investigate the effects of prenatal HI on oxidative stress, nitric oxide production, and motor and behavior responses in adult rats. HI was induced by clamping the uterine arteries of pregnant rats for 45 minutes, previously anesthetized with tribromoethanol injected intraperitoneally (300mg/kg), on the 18th day of gestation (HI group) (3). In the other group of females the surgery was the same, but without clamping the arteries (SHAM group - SH). The weight of the male pups was measured weekly until 90 days postnatal (P90). They were measured for motricity and anxiety by the open field test (OFT) and the plus maze, respectively. The animals in P90 were anesthetized with thiopental and blood collected from the abdominal aorta. Anti-oxidant enzyme catalase activity, thiobarbituric acid reactive substances-TBARS and nitrite (Griess reagent) formation in the serum were measured. The experimental procedures were approved by the Institutional Animal Care and Use Committee (CEA/051/2009) and were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Data were compared with a one-way ANOVA, expressed by mean± SEM, and significance level was set at 5%, SH n=5 and HI n=10. The HI animals showed reduced weight in comparison with the SH (HI= 8,59±0,14, SH= 8,59±0,19) up to 23 days post-natal. HI adult male rats had reduced motor activity in the OFT (HI=34,19 vs SH=62,34) and did not show increased anxiety compared with the SH group. The oxidative stress marker, evaluated through TBARS formation (ηmol TBA/mg proteins), and anti-oxidant activity of catalase (U/mg of protein) were not modified systemically by HI (TBARS: HI=0,04 vs SH=0,03 and catalase: HI=0,0191 vs SH=0,0122). In relation to nitrite production (mMol/ mg of protein), no significant differences were shown between the HI and sham groups (HI=0,407 vs SH=0,427). Our findings showed that HI impairs motor activity, not affect anxiety and did not cause oxidative stress or affect systemic nitric oxide. Future studies are needed to investigate the relationship of prenatal HI and cardiovascular risk in adults.
Where applicable, experiments conform with Society ethical requirements