ABSTRACT
Abstract Background: Prenatal stress may increase risk of developing cardiovascular disorders in adulthood. The cardiotoxic effects of catecholamines are mediated via prolonged adrenergic receptor stimulation and increased oxidative stress upon their degradation by monoamine oxidase A (MAO-A). Objectives: We investigated long-term effects of prenatal stress on β (1, 2, 3) adrenergic receptors and MAO-A gene expression in the hearts of adult rat offspring. Methods: Pregnant rats were exposed to unpredictable mild stress during the third week of gestation. RNA was isolated from left ventricular apex and base of adult offspring. Quantitative PCR was used to measure gene expression in collected ventricular tissue samples. The level of significance was set to p < 0.05. Results: β3 adrenergic receptor mRNA was undetectable in rat left ventricle. β1 adrenergic receptor was the predominantly expressed subtype at the apical and basal left ventricular myocardium in the control females. Male offspring from unstressed mothers displayed higher apical cardiac β1 than β2 adrenergic receptor mRNA levels. However, β1 and β2 adrenergic receptor mRNAs were similarly expressed at the ventricular basal myocardium in males. Unlike males, prenatally stressed females exhibited decreased β1 adrenergic receptor mRNA expression at the apical myocardium. Prenatal stress did not affect cardiac MAO-A gene expression. Conclusions: Collectively, our results show that prenatal stress may have exerted region- and sex-specific β1 and β2 adrenergic receptor expression patterns within the left ventricle.
Resumo Fundamento: Estresse pré-natal pode aumentar os riscos de desenvolver doenças cardiovasculares na idade adulta. Os efeitos cardiotóxicos de catecolaminas são mediados pela estimulação prolongada dos receptores adrenérgicos e pelo aumento do estresse oxidativo após sua degradação pela monoamina oxidase A (MAO-A). Objetivos: Investigamos os efeitos a longo prazo de estresse pré-natal nos receptores β (1, 2, 3) adrenérgicos e na expressão do gene MAO-A nos corações da prole adulta de ratos. Método: Ratas prenhes foram expostas a estresse crônico moderado imprevisível durante a terceira semana de gestação. O RNA foi isolado do ápice e da base do ventrículo esquerdo da prole adulta. Utilizou-se PCR quantitativa em tempo real para medir a expressão gênica nas amostras de tecido ventricular coletadas. O nível de significância foi estabelecido em p < 0,05. Resultados: Foi indetectável o mRNA do receptor adrenérgico β3 no ventrículo esquerdo dos ratos. O receptor adrenérgico β1 foi o subtipo mais expresso no miocárdio ventricular esquerdo apical e basal nas fêmeas controle. A prole masculina das mães não estressadas apresentou níveis cardíacos apicais de mRNA do receptor adrenérgico β1 mais altos do que os de β2. Porém, mRNAs dos receptores adrenérgicos β1 e β2 foram expressos de forma semelhante no miocárdio basal ventricular na prole masculina em geral. Ao contrário da prole masculina, a prole feminina exposta ao estresse pré-natal exibiu uma expressão diminuída do mRNA do receptor adrenérgico β1 no miocárdio apical. O estresse pré-natal não afetou a expressão gênica de MAO-A cardíaca. Conclusões: Coletivamente, nossos resultados mostram que estresse pré-natal pode ter exercido padrões de expressão região- e sexo-específica dos receptores adrenérgicos β1 e β2 no ventrículo esquerdo.
Subject(s)
Animals , Female , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Stress, Psychological/metabolism , Pregnancy, Animal/psychology , Receptors, Adrenergic, beta/analysis , Monoamine Oxidase/analysis , Myocardium/metabolism , Prenatal Exposure Delayed Effects/psychology , Reference Values , Stress, Psychological/genetics , Time Factors , RNA, Messenger/analysis , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/psychology , Gene Expression , Sex Factors , Receptors, Adrenergic, beta/genetics , Rats, Wistar , Adrenocorticotropic Hormone/blood , Real-Time Polymerase Chain Reaction , Heart Ventricles/metabolism , Monoamine Oxidase/genetics , Mothers/psychologyABSTRACT
Abstract Background: Radiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE) concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7)- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. Results: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH) expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT) were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7) and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. Conclusion: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7)-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.
Resumo Fundamentos: A denervação simpática renal por radiofrequência (DSR) mostra redução eficaz da pressão arterial (PA) de pacientes hipertensos, ainda que os mecanismos específicos permaneçam obscuros. Objetivo: Fizemos a hipótese de que níveis alterados de noradrenalina (NA) e mudanças nas enzimas relacionadas à NA e enzima conversora de angiotensina 2 (ECA-2), angiotensina (Ang)-(1-7) e receptor Mas são mediadores dos efeitos antihipertensivos da DSR. Métodos: Foram avaliados os valores médios de pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e pressão arterial média (PAM) no início e durante o seguimento. Foram medidas as concentrações plasmática e renal de noradrenalina (NA) por cromatografia líquida de alta eficiência com detecção eletroquímica, e os níveis de enzima relacionada à NA e ECA2-Ang-(1-7)-Mas através de PCR em tempo real, Western blot e imunohistoquímica ou Elisa em um modelo canino de hipertensão que recebeu ração rica em gordura e foi tratado com DSR. Os parâmetros também foram determinados em um grupo de cirurgia simulada submetido à arteriografia renal e em um grupo controle que recebeu dieta normal. Resultados: DSR causou diminuição da PAS, PAD, PAM e das concentrações plasmática e renal de NA. Em comparação ao grupo placebo, a expressão da tirosina hidroxilase (TH) renal foi menor e a da renalase foi maior no grupo DSR. Em comparação ao grupo controle, os níveis de TH renal e de catecol-o-metil-transferase (COMT) foram maiores e os de renalase foram menores no grupo cirurgia simulada. Além disso, os níveis renais de ECA2, Ang-(1-7) e Mas foram maiores no grupo DSR do que no grupo cirurgia simulada, que, por sua vez, foram menores do que no grupo controle. Conclusões: A DSR mostra efeitos anti-hipertensivos com redução da NA e ativação da ECA2-Ang-(1-7)-Mas, o que indica que pode contribuir com o efeito anti-hipertensivo da DSR.
Subject(s)
Animals , Dogs , Sympathectomy/methods , Catheter Ablation/methods , Hypertension/surgery , Kidney/surgery , Kidney/innervation , Peptide Fragments/analysis , Reference Values , Renal Artery/surgery , Tyrosine 3-Monooxygenase/analysis , Body Weight , Angiotensin I/analysis , Immunohistochemistry , Random Allocation , Catechol O-Methyltransferase/analysis , Blotting, Western , Reproducibility of Results , Chromatography, High Pressure Liquid , Treatment Outcome , Peptidyl-Dipeptidase A/analysis , Models, Animal , Norepinephrine Plasma Membrane Transport Proteins/analysis , Diet, High-Fat , Monoamine Oxidase/analysisABSTRACT
The present study was undertaken to investigate the effect of chronic administration of lead and cadmium on the activity of monoamine oxidase [MAO] in different central nervous system regions [CNS] of male guinea pigs. Lead and cadmium was intraperitoneally injected at dose level [30 mg/kg. body weight]and[1 mg/kg.] respectively as lead acetate and cadmium chloride daily for, two, four, six and eight weeks. The activity of monoamine oxidase [MAO] was determined in the cerebral cortex, caudate putamen, thalamus, hypothalamus, superior colliculus, inferior colliculus cerebellum, pons, medulla and spinal cord in male guinea pig CNS. Lead and cadmium induced a general variable changes in the level of the membrane bound enzyme [MAO] in most CNS regions and in turn affecting both cholinergic and adrenergic neurotransmitters. These results suggest that lead and cadmium may exerts neurotoxic effect by altering certain membrane bound enzymes and may cause oxidative stress that could lead to neurodegenerative diseases
Subject(s)
Male , Animals, Laboratory , Cadmium/adverse effects , Monoamine Oxidase/analysis , Brain , Guinea Pigs , Male , Oxidative Stress , Neurodegenerative DiseasesABSTRACT
Quassin, a mosquito larvicide isolated from Quassia amara, inhibits tyrosinase activity in the larvae of Culex quinquefasciatus. Since tyrosinase is directly involved in sclerotisation of the cuticle, it is suggested that quassin, as a larvicide, inhibits development of the cuticle. In presence of quassin phenylalanine, tyrosine and L-dopa levels were increased in larvae. In the larval stages, mosquitoes have a high concentration of phenylalanine and tyrosine with the level of the latter being very high just before pupation and then declines sharply. Monoamine oxidase (MAO), an enzyme directly involved in the metabolism of catecholamines, remained unaffected by quassin, in fact the level of adrenaline also remained unchanged in larvae during quassin poisoning. MAO showed high variation in its activity between synthetic and natural substrates. Tyramine is not a substrate for MAO. Tyrosinase activity was high in developing stages and negligibly low in adults and showed specificity to L-dopa. Phenylalanine and tyramine are unaffected by tyrosinase. Blood feeding did not influence the activity of both these enzymes.
Subject(s)
Animals , Catecholamines/metabolism , Culex/metabolism , Female , Glaucarubin/analogs & derivatives , Insecticides/pharmacology , Male , Monoamine Oxidase/analysis , Monophenol Monooxygenase/analysis , QuassinsABSTRACT
Platelet monoamine oxidase activity was assessed in 50 schizophrenics and 30 controls. The platelet MAO activity was significantly lower in schizophrenics compared to controls. There was no significant difference between paranoid and disorganized schizophrenics regarding platelet MAO activity. Schizophrenics with negative symptoms showed significantly lower platelet MAO activity than those with positive symptoms. The platelet MAO activity in patients with positive family history of schizophrenia was significantly lower than schizophrenics with negative family history
Subject(s)
Risk Factors , Schizophrenia/classification , Monoamine Oxidase/analysis , Platelet CountABSTRACT
The paper describes the effect of two drugs, (Eltroxine and Neomercazol) on the nature and activity of monoamine oxidase (MAO) in albino rats. Four organs namely liver, kidney, brain and heart were examined from this point of view. Biological activity measurements were done using tyramine hydrochloride as the substrate. The liver MAO from normal as well as the drug treated rats were subjected to DEAE gel filtration studies. These investigations show that there is a significant difference in the biological activity as well as in the actual nature of the enzyme as a result of treatment with the drugs mentioned above.