Adrenoceptores- alfa-1 envolvidos na contração da aorta abdominal em modelo experimental de pré-eclâmpsia em ratas
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Data
2016-03-04
Autores
Silva, Katiussia Pinho da [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A Pré-eclâmpsia (PE) é uma desordem hipertensiva gestacional, cuja fisiopatologia tem sido atribuída a forte resposta inflamatória, disfunção endotelial, agregação plaquetária e aumento da resistência vascular. Estudos com PE relatam inadequado aumento na ação de vários vasoconstritores, incluindo endotelina, adenosina, angiotensina II, e noradrenalina ocasionando aumento da pressão arterial. De fato, o sistema nervoso autonômo simpático através do neurotransmissor noradrenalina regula a pressão arterial mediante a ativação dos adrenoceptores-alfa-1 (ARs-alfa-1). No presente estudo, foi investigado através do uso de agonistas e antagonistas seletivos os subtipos de ARs-alfa1 envolvidos na contração da aorta abdominal de ratas prenhes submetidas à um modelo experimental de PE por redução da pressão de perfusão uterina (RUPP), e esses receptores foram comparados com aqueles envolvidos na contração da artéria de ratas virgens. Os resultados indicam que as contrações da artéria aorta abdominal de ratas virgens em resposta à noradrenalina resultam da ativação de AR-alfa-1A e AR-alfa-1D, mas que na artéria da fêmea há uma maior contribuição de AR-alfa-1A do que na respectiva artéria de machos. Além disso, a prenhez induziu plasticidade nos subtipos de ARs-alfa-1 envolvidos na contração da artéria aorta abdominal, uma vez que houve menor participação de AR-alfa-1A nas contrações de ratas prenhes do que aquela observada na artéria de ratas virgens. Por outro lado, na artéria aorta abdominal de fêmeas submetidas à RUPP agonistas e antagonistas seletivos mostraram comportamento complexo que, apesar de indicar o envolvimento de AR-alfa-1A e AR-alfa-1D, indica algum tipo de interação próxima entre esses subtipos. O presente estudo mostra que tanto a prenhez quanto a cirurgia de redução da pressão de perfusão uterina induz plasticidade nos ARs-alfa1 envolvidos na contração da artéria aorta abdominal ressaltando a necessidade de que o estudo de drogas potencialmente úteis no tratamento de uma determinada patologia seja feito em modelos experimentais que mimetizem a situação terapêutica. Portanto, será importante investigar a capacidade de diferentes antagonistas de ARs-alfa1 reduzirem a pressão arterial elevada das ratas submetidas à esse modelo experimental de pré-eclâmpsia.
Preeclampsia (PE) is a gestational hypertensive disorder, for which the physiopathology has been attributed to an intense inflammatory response, endothelial disfunction, platelet aggregation and increased vascular resistance. Previous studies reported that in PE there is an inadequate increase in the action of several vasoconstrictors, including endothelin, adenosine, angiotensin II and noradrenaline. In fact, the sympathetic nervous system by releasing the neurotransmitter noradrenaline regulates the arterial pressure through activation of 1-adrenoceptors (1-ARs). The present study investigated the 1–ARs subtypes involved in the contractions of the abdominal aortae from pregnant rats submitted to an experimental model of PE, the reduced in uterine perfusion pressure (RUPP), compared these receptors with those involved in the contractions of abdominal aortae from non-pregnant (virgin) and pregnant female rats. The results indicate that there are both 1A–ARs and 1D– ARs in abdominal aortae from non pregnant females, but that the 1A–ARs is more important in the contraction of the female than in the contraction of the respective artery from male rats. Pregnancy induces plasticity in the 1 – ARs of the abdominal aortae, since there was a less significant participation of 1A-AR in the contraction of abdominal aortae from pregnant rats than in the artery of virgin females. In the other hand, selective agonists and antagonists presented complex behaviours in the abdominal aorta from pregnant females submitted to the RUPP model, indicating that there must be a close interaction between 1A-AR e 1D-AR in the contraction of this artery. The present study shows that either pregnancy or RUPP model induces plasticity in the 1-ARs of the abdominal aortae highlighting the need that the study of potentially useful drugs to treat a certain disease must be performed in experimental models that mimic the therapeutic condition. It will be important to investigate the ability of 1-ARs antagonists to reduce the arterial pressure of rats submitted to this experimental model of PE.
Preeclampsia (PE) is a gestational hypertensive disorder, for which the physiopathology has been attributed to an intense inflammatory response, endothelial disfunction, platelet aggregation and increased vascular resistance. Previous studies reported that in PE there is an inadequate increase in the action of several vasoconstrictors, including endothelin, adenosine, angiotensin II and noradrenaline. In fact, the sympathetic nervous system by releasing the neurotransmitter noradrenaline regulates the arterial pressure through activation of 1-adrenoceptors (1-ARs). The present study investigated the 1–ARs subtypes involved in the contractions of the abdominal aortae from pregnant rats submitted to an experimental model of PE, the reduced in uterine perfusion pressure (RUPP), compared these receptors with those involved in the contractions of abdominal aortae from non-pregnant (virgin) and pregnant female rats. The results indicate that there are both 1A–ARs and 1D– ARs in abdominal aortae from non pregnant females, but that the 1A–ARs is more important in the contraction of the female than in the contraction of the respective artery from male rats. Pregnancy induces plasticity in the 1 – ARs of the abdominal aortae, since there was a less significant participation of 1A-AR in the contraction of abdominal aortae from pregnant rats than in the artery of virgin females. In the other hand, selective agonists and antagonists presented complex behaviours in the abdominal aorta from pregnant females submitted to the RUPP model, indicating that there must be a close interaction between 1A-AR e 1D-AR in the contraction of this artery. The present study shows that either pregnancy or RUPP model induces plasticity in the 1-ARs of the abdominal aortae highlighting the need that the study of potentially useful drugs to treat a certain disease must be performed in experimental models that mimic the therapeutic condition. It will be important to investigate the ability of 1-ARs antagonists to reduce the arterial pressure of rats submitted to this experimental model of PE.
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Palavras-chave
Pré-eclâmpsia, Adrenoceptores-alfa-1, Aorta abdominal, Preeclampsia, Alfa-1-Adrenoceptors, Abdominal Aortae