ABSTRACT
o sistema nervoso autônomo contribui diretamente para uma série de atividades biológicas e está envolvido em inúmeras doenças. A hiperatividade simpática é um dos vários mecanismos envolvidos na patogênese da hipertensão arterial sistêmica (HAS) primária. A transmissão da informação nervosa através de sinapses é mediada por agentes químicos específicos conhecidos como neurotransmissores, representados pela acetilcolina e pelas catecolaminas. O bloqueio dos receptores pré e pós-sinapse permite que a ação de fárrnacos alcance sua plenitude no controle dos portadores de hiperati vidade simpática. Um percentual significativo de hipertensos são resistentes ao tratamento farrnacológico. A denervação simpática renal surgiu como estratégia terapêutica adjunta no controle de hipertensos resistentes ao tratamento clínico. Nos últimos cinco anos, diversos estudos demonstraram resultados consistentes na redução da pressão arterial. Diversas outras condições clínicas associam-se à hiperatividade do sistema adrenérgico, tais como a insuficiência cardíaca, o diabetes mellitus, a doença renal crônica, a síndrome da apneia e hipopneia obstrutiva do sono e as arritmias cardíacas. Nestes contextos, a redução da atividade simpática renal também mostrou-se ser benéfica em estudos clínicos iniciais. Uma variedade de dispositivos dedicados foram e estão sendo desenvolvidos com o objetivo de ampliar a segurança e a eficácia do método, além de facilitar o procedimento. Estudos multicêntricos, prospectivos, randomizados e controlados em andamento investigam desfechos como mortalidade cardiovascular, infarto agudo do miocárdio e acidente vascular cerebral em longo prazo.
The autonomic nervous system contributes directly to a number of biological activities and is involved in numerous diseases. Sympathetic hyperactivity is one of several mechanisms involved in the pathogenesis of primary hypertension. The transmission through the nerve synapses is mediated by specific chemical agents known as neurotransmitters represented by the acetylcholine and catecholarnine. Blockade of specific pre-and post-synapse receptors allows the treatment of patients with sympathetic hyperactivity. A large proportion of hypertensive patients are resistant to pharmacological treatment. Renal sympathetic denervation emerged as adjunctive therapeutic strategy in controlling hypertension resistant to medical treatrnent. ln the last five years, several studies have shown consistent results in lowering blood pressure. Several other clinica! conditions are associated with hyperactivity of the adrenergic system such as heart failure, diabetes mellitus, chronic kidney disease, obstructive sleep apnea, polycystic ovary syndrome and cardiac arrhythrnias. ln these contexts, the reduction in renal sympathetic activity also proved to be beneficial in initial clinical studies. A substantial variety of dedicated devices have been developed in order to reduce variability between operators, reduce renal artery manipulation, improve vessel contact, reduce radiation exposure and procedure time, and therefore improving safety and efficacy. Mu!ticenter, prospective, randomized, controlled trials are ongoing to investigate long term outcomes such as cardiovascular mortality, acute myocardial infarction and stroke.
Subject(s)
Humans , Catheter Ablation/methods , Hypertension/complications , Hypertension/physiopathology , Heart Failure/diagnosis , Heart Failure/physiopathology , Drug Therapy/methods , Autonomic Nervous System/physiopathology , Sympathetic Nervous System/physiopathology , Adrenergic beta-Antagonists , Clonidine/adverse effects , Denervation , Cross-Over Studies , Atrial Fibrillation/physiopathology , Guanabenz , Guanfacine/adverse effects , Methyldopa/adverse effects , Kidney , Sympathectomy/methodsABSTRACT
Experimental hypertension, was induced in rats by intramuscular injection of desoxycorticosterone [DOCA] in a dose of 50 mg/kg body weight/week for six weeks, in addition to salt in drinking water. Guanfacine was given to normotensive and hypertensive rats intraperitoneally in a daily dose of 0.09 and 0.18 mg/kg body weight for 30 days. Induction. of hypertension resulted in significant reduction in the neurotransmitter gamma aminobutyric acid [GABA] concentration in the brain, hypertrophy of the cardiac muscle and nephrosclerosis with impaired renal function. However, these histophathological and biochemical changes were paradoxically decreased after giving guarifacine in a daily dose of 0.09 mg/kg body weight for 30 days, as a result of marked decrease of blood pressure. The hypertensive rats treated with 0.18 mg/kg body weight of guanfacine for 30 days showed marked increase in the incidence and severity of cardiac and renal histopathological changes, due to the combined toxic effect of guanfacine and hypertension. The increased GABA concentration in the brain and the reduction in blood pressure after giving the drug were more significant with the low dose. In normotensive groups, rats treated with guanfacine in a daily dose of 0.18mg/kg body weight for 30 days showed moderate renal toxicity, while no biochemical or histopathological changes were observed with 0.09 mg/kg body weight of guanfacine. The two doses of guanfacine induced insignificant changes in both blood pressure and GABA concentration in the brain as compared to control non-treatment rats. Thuse law dose of guanfacine is considered more effective and safe and so it is superior to high dose in the ambulatory treatment of hypertension