Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Original Investigation

Changes in gap junction proteins Connexin30.2 and Connexin40 expression in the sinoatrial node of rats with dexmedetomidine-induced sinus bradycardia

Alterações na expressão das proteínas de junção comunicante Connexin30.2 e Connexin40 no nó sinoatrial de ratos com bradicardia sinusal induzida por dexmedetomidina

Yong-Qiang Yin, Yi Zhong, Yu Zhu, Lei Tian

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Dexmedetomidine (Dex) is widely used, and its most common side effect is bradycardia. The complete mechanism through which Dex induces bradycardia has not been elucidated. This research investigates the expression of gap junction proteins Connexin30.2 (Cx30.2) and Connexin40 (Cx40) within the sinoatrial node of rats with Dex-induced sinus bradycardia.

Eighty rats were randomly assigned to five groups. Saline was administered to rats in Group C. In the other four groups, the rats were administered Dex to induce bradycardia. In groups D1 and D2, the rats were administered Dex at a loading dose of 30 μ−1 and 100 μ−1 for 10 min, then at 15 μ−1.h−1 and 50 μ−1.h−1 for 120 min separately. The rats in group D1A and D2A were administered Dex in the same way as in group D1 and D2; however, immediately after the administration of the loading dose, 0.5 mg atropine was administered intravenously, and then at 0.5−1.h−1 for 120 min. The sinoatrial node was acquired after intravenous infusion was completed. Quantitative real-time polymerase chain reaction and western blot analyses were performed to measure mRNA and protein expression of Cx30.2 and Cx40, respectively.

The expression of Cx30.2 increased, whereas the expression of Cx40 decreased within the sinoatrial node of rats with Dex-induced sinus bradycardia. Atropine reversed the effects of Dex on the expression of gap junction proteins.

Dex possibly altered the expression of gap junction proteins to slow down cardiac conduction velocity in the sinoatrial node.


Autonomic nerve system;  Connexins;  Dexmedetomidine;  Sinus bradycardia  


Justificativa: A dexmedetomidina (Dex) é amplamente utilizada e seu efeito colateral mais comum é a bradicardia. O mecanismo completo pelo qual Dex induz bradicardia não foi elucidado. Esta pesquisa investiga a expressão das proteínas de junção comunicante Connexin30.2 (Cx30.2) e Connexin40 (Cx40) no nodo sinoatrial de ratos com bradicardia sinusal induzida por Dex. Métodos: Oitenta ratos foram distribuídos aleatoriamente em cinco grupos. A solução salina foi administrada aos ratos do Grupo C. Nos outros quatro grupos, os ratos receberam Dex para induzir bradicardia. Nos grupos D1 e D2, os ratos receberam Dex em uma dose de ataque de 30 μg/kg-1 e 100 μg/kg-1 por 10 min, depois a 15 μg/kg-1/he 50 μg/kg-1/h-1 por 120 min separadamente. Os ratos do grupo D1A e D2A receberam Dex da mesma forma que no grupo D1 e D2; entretanto, imediatamente após a administração da dose de ataque, foi administrado 0,5 mg de atropina por via intravenosa e, em seguida, 0,5 mg/kg-1/h-1 por 120 min. O nó sinoatrial foi adquirido após o término da infusão intravenosa. A reação em cadeia da polimerase quantitativa em tempo real e análises de Western blot foram realizadas para medir a expressão de mRNA e proteína de Cx30.2 e Cx40, respectivamente. Resultados: A expressão de Cx30.2 aumentou, enquanto a expressão de Cx40 diminuiu dentro do nó sinoatrial de ratos com bradicardia sinusal induzida por Dex. A atropina reverteu os efeitos de Dex na expressão de proteínas de junções comunicantes. Conclusão: Dex possivelmente alterou a expressão de proteínas de junções comunicantes para diminuir a velocidade de condução cardíaca no nó sinoatrial.


Sistema nervoso autônomo; Conexinas; Dexmedetomidina; Bradicardia sinusal


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