Moderate hyperhomocysteinemia provokes dysfunction of cardiovascular autonomic system and liver oxidative stress in rats.
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 100mg/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. Signals were 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=6.24mmHg(2)) 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.
Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil; Instituto de Nutrição Josué de Castro, Universidade Federal do Rio de Janeiro, Brazil.
R H
RH
Mendes
Hospital Materno Infantil, Universidade Federal do Maranhão, Brazil; Unidade de Hipertensão, Instituto do Coração, Universidade de São Paulo, Brazil.
C
C
Mostarda
Unidade de Hipertensão, Instituto do Coração, Universidade de São Paulo, Brazil.
G O
GO
Candido
Unidade de Hipertensão, Instituto do Coração, Universidade de São Paulo, Brazil; Programa de Pós-Graduação em Ciências da Saúde, Universidade Santo Amaro, Brazil.
I C
IC
Moraes-Silva
Departamento de Biociências, UNIFESP, SP, Brazil.
V
V
D'Almeida
Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil.
A
A
Belló-Klein
Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil; Unidade de Hipertensão, Instituto do Coração, Universidade de São Paulo, Brazil.
M C
MC
Irigoyen
Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil. Electronic address: krigatto@gmail.com.
K
K
Rigatto
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D002374:Catalase / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000633:toxicity; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis
D017382:Reactive Oxygen Species; D008715:Methionine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
Autonomic imbalance; Homocysteine; Liver oxidative stress