Effect of ephedrine hydrochloride on regulation of body fluid metabolism and AQP1 and AQP2 in a rabbit model of mechanical ventilation

Abstract

Objective: Ephedrine hydrochloride (EH) is a major component from Ephedra sinica STAPF, which is used as a traditional Chinese herbal medicine. This study was designed to investigate the effect of EH on water metabolism and further explore the relevant signaling pathway of body fluid regulation in “lung governing regulation of water passage” using a rabbit model of mechanical ventilation. The molecular mechanism of the EH effect in the kidney was also investigated. Methods: Rabbits were randomly divided into a control group, model group, EH group, and dexmedetomidine hydrochloride (DH) group. Urine volume was measured by the intubation method and pathologic changes in lung and renal tissue were measured by hematoxylin and eosin staining. Nitric oxide (NO) production in lung, serum, and kidney were analyzed using chemical methods. An ELISA was used to analyze angiotensin II (Ang II), antidiuretic hormone (ADH), prostaglandin E2 (PGE2), atrial natriuretic peptide (ANP), and endothelin-1 (ET-1) levels in the lung, serum, and kidney. Aquaporin-1 (AQP1) and aquaporin-2 (AQP2) mRNA and protein expression in the kidney was determined using qRT-PCR and immunohistochemistry. Results: EH significantly inhibited the decrease in the total urine volume in the third and fourth stages, and displayed significant regulatory effects on NO, Ang II, ADH, PGE2, ANP, and ET-1 in serum, lung, and renal tissues compared with the model group. In the kidney, AQP1 and AQP2 mRNA and protein expression in the EH group were remarkably down-regulated compared with the model group. Conclusion: EH exerted a regulatory effect on water metabolism by diffusing the lung and increased urine volume in the rabbit model, which was consistent with the decrease in kidney AQP1 and AQP2 expression levels that led to an increase in urine volume. EH could assist with DH to exert a protective effect on the clinical application of mechanical ventilation. Keywords: Mechanical ventilation, Ephedrine hydrochloride, Dexmedetomidine hydrochloride, Humoral regulation