Changes in expression of Cx45 and Cx40 in sinoatrial node during dexmedetomidine-induced sinus bradycardia in rats

Abstract

Objective To evaluate the changes in the expression of Cx45 and Cx40 in the sinoatrial node during dexmedetomidine-induced sinus bradycardia in rats. Methods Forty healthy Sprague-Dawley rats, weighing 250-300 g, were divided into 5 groups (n=8 each) using a random number table method: control group (group C), low-dose dexmedetomidine group (group D1), high-dose dexmedetomidine group (group D2), low-dose dexmedetomidine plus atropin group (group D1A), and high-dose dexmedetomidine plus atropin group (group D2A). Normal saline was intravenously infused in group C. Dexmedetomidine was intravenously infused for 10 min as a loading dose of 20 and 120 μg/kg, followed by an infusion of 10 and 60 μg·kg-1·h-1 for 110 min in D1 and D2 groups, respectively.In D1A and D2A groups, dexmedetomidine was correspondingly given according the method previously described in D1 and D2 groups, and in addition atropin 0.5 mg was intravenously injected at the end of infusing the loading dose of dexmedetomidine. Heart rate(HR), mean arterial pressure(MAP) and SpO2 were recorded before giving dexmedetomidine and at 10, 60 and 120 min after giving dexmedetomidine, and the development of bradycardia was recorded.The sinoatrial node tissues were obtained at the end of administration for determination of the expression of Cx45 and Cx40 protein and mRNA by Western blot and real-time polymerase chain reaction, respectively. Results The incidence of bradycardia was 100% in D1 and D2 groups and 0 after using atropin in D1A and D2A groups.Compared with group C, HR and MAP were significantly decreased in the other four groups, the expression of Cx45 protein and mRNA was up-regulated, the expression of Cx40 protein and mRNA was down-regulated in D1 and D2 groups (P 0.05). Compared with group D1, HR and MAP were significantly increased, the expression of Cx45 protein and mRNA was down-regulated, and the expression of Cx40 protein and mRNA was up-regulated in group D1A (P<0.05). Compared with group D2, HR and MAP were significantly increased, the expression of Cx45 protein and mRNA was down-regulated, and the expression of Cx40 protein and mRNA was up-regulated in group D2A (P<0.05). Conclusion The mechanism by which dexmedetomidine induces sinus bradycardia may be related to up-regulated expression of Cx45 and down-regulated expression of Cx40, and the autonomic nervous activity is involved in dexmedetomidine-induced regulation of Cx45 and Cx40 expression in rats. Key words: Dexmedetomidine; Bradycardia; Sinus node; Connexins