Moderate hyperhomocysteinemia provokes dysfunction of cardiovascular autonomic system and liver oxidative stress in rats (2013)

17 de outubro de 2013 às 14:04

Autores: R.H. Mendes1,6, C. Mostarda2,3, G.O. Candidoc3, I.C. Moraes-Silva3,7, V. D’Almeida5, A. Belló-Kleina1, M.C. Irigoyen1,3, K. Rigatto1,4

1 Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil
2 Hospital Materno Infantil, Universidade Federal do Maranhão, Brazil
3 Unidade de Hipertensão, Instituto do Coração, Universidade de São Paulo, Brazil
4 Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil
5 Departamento de Biociências, UNIFESP, SP, Brazil
6 Instituto de Nutrição Josué de Castro, Universidade Federal do Rio de Janeiro, Brazil
7 Programa de Pós-Graduação em Ciências da Saúde, Universidade Santo Amaro, Brazil


Hyperhomocysteinemia (HHcy) is associated with cardiovascular disease, atherosclerosis and reactive oxygen species generation. Thus, our aim was to investigate whether there was an association between HHcy, blood pressure, autonomic control and liver oxidative stress. Male Wistar rats were divided into 2 groups and treated for 8weeks: one group (control, CO) received tap water, while the other group (methionine, ME) was given a 100 mg/kg of methionine in water by gavage. Two catheters were implanted into the femoral artery and vein to record arterial pressure (AP) and heart rate (HR) and drug administration. Signalswere recorded by a data acquisition system. Baroreflex sensitivity was evaluated by HR responses to AP changes induced by vasoactive drugs. HR variability and AP variability were performed by spectral analysis in time and frequency domains to evaluate the contribution of the sympathetic and parasympathetic modulation. Lipid peroxidation and antioxidant enzyme activities were evaluated by measuring superoxide dismutase, catalase and glutathione peroxidase in liver homogenates. The ME group presented a significant increase in systolic arterial pressure (118 ± 9 vs 135±6mmHg), diastolic arterial pressure (81±6 vs. 92±4) and mean arterial pressure (95±7 vs. 106 ± 6). In addition, pulse interval variability presented a significant decrease (41%),while the low frequency component of AP was significantly increased (delta P=6.24mmHg2) in the ME group. We also found a positive association between lipid peroxidation and cardiac sympathetic modulation, sympathetic and vagal modulation ratio and systolic pressure variability. Collectively, these findings showed that HHcy induced dysfunction of cardiovascular autonomic system and liver oxidative stress.

Keywords: Homocysteine, Autonomic imbalance, Liver oxidative stress