Efeitos bioquímicos e imunológicos da terapia anti-hipertensiva
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Date
2009
Authors
Brandão, Sergio Augusto Bueno [UNIFESP]
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Fonseca, Francisco Antonio Helfenstein [UNIFESP]
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Tese de doutorado
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Abstract
Objetivos: Lipoproteínas oxidadas e anticorpos (Abs) anti-LDL oxidada (antiLDLox)
foram detectados no plasma em resposta à elevação da pressão arterial,
sugerindo a participação do sistema imune adaptativo. Postulamos que o
tratamento da hipertensão possa modificar a resposta imune diminuindo o
estímulo oxidativo. Analisamos os títulos de Abs anti-LDLox após adequado
controle da hipertensão arterial. Métodos: Títulos de Abs anti-LDLox foram
examinados em pacientes com hipertensão arterial no estágio 1 (n=94), sem
manifestação clínica prévia de aterosclerose ou fatores de risco clássicos para a
doença coronariana e isentos de medicações anti-hipertensivas. Pacientes foram
distribuídos aleatoriamente para terapia com perindopril, hidroclorotiazida ou
indapamida por 12 semanas, com adição de perindopril, se necessário para
adequado controle pressórico. Títulos de Abs anti-LDLox foram mensurados por
ELISA. Resultados: O tratamento anti-hipertensivo reduziu as pressões arteriais
casuais e as obtidas pela MAPA (p<0,0005), diminuiu os níveis plasmáticos de
substâncias reativas ao ácido tiobarbitúrico (p<0,05) e aumentou os títulos dos Ab
anti-LDLox (p<0,005) e a dilatação mediada pelo fluxo (p<0,0005),
independentemente do tratamento instituído. Conclusões: Aumento nos títulos de
Abs anti-LDLox após terapia anti-hipertensiva ao lado de melhor função endotelial
e diminuição do estresse oxidativo sugerem que a despeito de maior estímulo
oxidativo estar presente na hipertensão, os Abs anti-LDLox podem ser potenciais
biomarcadores protetores para monitorizar o tratamento da hipertensão.
Objectives: Oxidized lipoproteins and autoantibodies anti-oxidized LDL (antioxLDL) have been detected in human plasma in response to blood pressure elevation. Thus, treatment of hypertension, by decreasing the stimuli for oxidation, may have an effect on the immune response. We aimed to assess early changes on anti-LDLox Abs after blood pressure control. Methods: Titers of human antioxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n=94), in primary prevention of coronary disease, with no other risk factors, and naïve of anti-hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide or indapamide during 12 weeks, with addition of perindopril if necessary to achieve blood pressure control. Abs anti-oxLDL were measured by ELISA. Results: Twelve-week antihypertensive treatment reduced both office-based and ambulatory blood pressure monitoring measurements (p<0.0005), decreased plasma TBARS (p<0.05), increased titers of anti-oxLDL Abs (p<0.005), and improved endothelial dependent vasodilation (p<0.0005), independently of treatment assignment. Conclusions: Increase in titers of Abs anti-oxLDL with improvement in endothelial function and reduction in oxidative stress suggests that albeit hypertension increases the oxidation stimuli, Abs anti-oxLDL may be protective and potential markers in the follow-up of hypertension treatment.
Objectives: Oxidized lipoproteins and autoantibodies anti-oxidized LDL (antioxLDL) have been detected in human plasma in response to blood pressure elevation. Thus, treatment of hypertension, by decreasing the stimuli for oxidation, may have an effect on the immune response. We aimed to assess early changes on anti-LDLox Abs after blood pressure control. Methods: Titers of human antioxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n=94), in primary prevention of coronary disease, with no other risk factors, and naïve of anti-hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide or indapamide during 12 weeks, with addition of perindopril if necessary to achieve blood pressure control. Abs anti-oxLDL were measured by ELISA. Results: Twelve-week antihypertensive treatment reduced both office-based and ambulatory blood pressure monitoring measurements (p<0.0005), decreased plasma TBARS (p<0.05), increased titers of anti-oxLDL Abs (p<0.005), and improved endothelial dependent vasodilation (p<0.0005), independently of treatment assignment. Conclusions: Increase in titers of Abs anti-oxLDL with improvement in endothelial function and reduction in oxidative stress suggests that albeit hypertension increases the oxidation stimuli, Abs anti-oxLDL may be protective and potential markers in the follow-up of hypertension treatment.
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Citation
BRANDÃO, Sergio Augusto Bueno. Efeitos bioquímicos e imunológicos da terapia anti-hipertensiva. 2009.93 f. Tese (Doutorado em Ciências) - Escola Paulista de
Medicina, Universidade Federal de São Paulo, São Paulo, 2009.