Participa????o dos receptores histamin??rgicos do tipo H1 e H2 presentes no n??cleo medial da am??gdala na resposta cardiovascular ao estresse.

Abstract

Situa????es de estresse repetido ou prolongado podem resultar em v??rios estados patol??gicos, como hipertens??o arterial, arritmias card??acas, infarto do mioc??rdio e at?? mesmo morte s??bita. Embora se tenha muita informa????o sobre o controle cerebral da press??o arterial, as respostas cardiovasculares ao estresse n??o s??o totalmente compreendidas. Dados da literatura mostram a import??ncia do n??cleo medial da amigdala (MeA) e da neurotrasmiss??o histamin??rgica no controle auton??mico das fun????es cardiovasculares, no entanto, n??o h?? estudos evidanciando o papel das vias histamin??rgicas no MeA nas adapta????es cardiovasculares evocada pelo estresse emocional. Desta forma, o objetivo desta pesquisa foi estudar a participa????o dos receptores H1 e H2 no MeA sobre as respostas cardiovasculares em ratos estressados e n??o-estressados. Ratos Wistar (280-320g) foram submetidos ?? cirurgia estereot??xica para canula????o bilateral do MeA. Passado cinco dias da estereotaxia, os animais foram submetidos a cateteriza????o da art??ria car??tida esquerda. Vinte e quatro horas ap??s a inser????o do cateter, foram iniciados os experimentos com a grava????o do registro da press??o arterial puls??til (PAP) dos animais em condi????es basais e em livre movimento em suas respectivas caixas de forma continuada. As drogas utilizadas para a microinje????o central foram a mepiramina (antagonista dos receptores H1) nos grupos experimentais I e III e a cimetidina (antagonista dos receptores H2) nos grupos experimentais II e IV. Nos grupos experimentais I e II, 15 min ap??s microinje????o central bilateral de mepiramina ou cimetidina respectivamente, em diferentes doses, os animais foram submetidos a estresse de restri????o de movimentos em tubos de polietileno, e a PAP foi registrada continuamente durante 45 min. Ap??s o per??odo de estresse, os animais foram realocados em suas caixas e a PAP foi registrada por mais 30 min. Nos grupos experimentais III e IV, ap??s as microinje????es centrais bilaterais no MeA, a PAP continuou sendo registrada por 75 min em animais sob condi????es basais e em livre movimento (n??o estressados). Os animais controles de todos os grupos experimentais receberam microinje????es de salina 0,9%. Os experimentos foram realizados entre 7h00min ??s 13h00min e os animais n??o tiveram acesso ?? ??gua ou ra????o durante o experimento. Os dados est??o expressos como m??dia??E.P.M das varia????es da PAM e FC. Microinje????es de mepiramina nas doses de 50, 100 e 200 nmol promoveu bloqueio dose-dependente da resposta hipertensiva evocada pelo estresse de restri????o. A cimetidina (100 e 200 nmol) atenuou a resposta hipertensiva ao estresse apenas na maior dose utilizada. A resposta anti-hipertensiva ao estresse foi maior nos animais que receberam microinje????es de mepiramina do que de cimetidina nas mesmas doses. Nenhuma das drogas alterou a resposta taquic??rdica t??pica do estresse. Mepiramina ou cimetidina foram incapazes de alterar a PAM ou a FC de animais n??o estressados. Os dados sugerem que as vias histamin??rgicas presentes no MeA medeiam a resposta pressora sem alterar a taquicardia evocadas pelo estresse de restri????o, ativando preferencialmente os receptores do tipo H1. Al??m disto, os dados confirmam a hip??tese de que a via histamin??rgica no MeA n??o exerce modula????o t??nica do sistema cardiovascular. A obten????o de dados adicionais relativos ao papel fisiol??gico dos receptores histamin??rgicos centrais no controle das fun????es cardiovasculares se reveste de grande import??ncia para as ci??ncias biol??gicas e para a cl??nica m??dica, principalmente quando vinculada ?? vari??vel estresse. Os resultados deste trabalho contribuem para o esclarecimento da participa????o destes receptores no controle das fun????es cardiovasculares.Repeated long lasting experiences of stress situations may result in various pathologic states such as arterial hypertension, cardiac dysrhythmias, myocardial stroke and even sudden death. Although there is a lot information about the neural control of the arterial blood pressure, especially by the brain stem and some other prosencephalic areas, stress-evoked cardiovascular responses are not totally understood. Previews studies shows the importance of the medial amygdala nucleus (MeA) and of the histaminergic neurotransmission on the autonomic control of cardiovascular functions, however there aren???t studies that evidence the role of the histaminergic pathways in MeA on emotional stress-evoked cardiovascular adaptations. Therefore, the aim of this study was investigate the participation of the histaminergic receptors H1 and H2 in MeA on the cardiovascular responses in stressed and non-stressed rats. Wistar rats (280-320g) were submitted to stereotaxic surgery for bilateral cannulation of MeA. Five days after surgery, animals were submitted to catheterization of the left carotid artery. Twenty four hours after catheter insertion, experiments were started and the pulsatile arterial pressure (PAP) of freely moving rats on basal conditions was recorded. Drugs used for central administration were mepyramine (H1 receptors antagonist) on experimental groups I and III and cimetidine (H2 receptors antagonist) on experimental groups II and IV. At experimental groups I and II, 15 min after central microinjections of mepyramine or cimetidine respectively, in different doses, the rats was submitted to restraint stress in a polyvinyl apparatus, and PAP were continuously recorded for 45 min. After stress period, rats were replaced in their own cages and an additional 30 min were recorded for PAP reestablishment. At experimental groups III and IV, after 30 min of basal recording, rats received bilateral central microinjections of mepyramine or cimetidine in a dose of 200 nmol, respectively, and an additional period of 75 min was recorded in freely moving rats on basal conditions. Saline 0,9% was administered as vehicle in control animals of all experimental groups. Mean arterial pressure (MAP) and heart rate (HR) were, then, calculated from the PAP signal. Experiments occurred between 7:00 and 13:00 and rat did not have access to water and food during the sessions. Data were expressed as mean??S.E.M. of MAP and HR variation. Mepyramine microinjections at doses of 50, 100 and 200 nmol promoted dose-dependent blockade of the restraint stress-evoked hypertensive response. Cimetidine (100 and 200 nmol) attenuated the hypertensive response to stress only at the highest dose administered. The anti-hypertensive response was bigger on animals which received mepyramine than cimetidine. Neither drugs altered the typical stress-evoked tachycardiac responses. Indeed, mepyramine or cimetidina were unable to modify the MAP or HR of freely moving rats on basal conditionals (non-stressed rats). These data suggest that histaminergic pathways in MeA mediates pressor responses without modifying the tachycardia promoted by restraint stress, activating preferentially H1 receptors. Besides, data corroborate to the hypothesis that histaminergic pathways in MeA do not plays tonic modulation of the cardiovascular system. Additional information acquired about physiologic role of central histaminergic receptor on the cardiovascular functions is important to biological science and to medical practice, especially when linked to the stress factor. These data contribute to clarify the role of these receptors on cardiovascular function