Effect of beta-adrenergic agonist on alveolar fluid clearance in rats

Objective

To investigate the effect and the associated mechanism of beta-adrenergic agonist on alveolar fluid clearance (AFC) in rats.

Methods

Forty-eight Sprague–Dawley male rats were randomly divided into six groups (normal control group, dobutamine group, amiloride [specific inhibitor of epithelial sodium channel] group, dobutamine + amiloride group, dobutamine + atenolol [specific beta-1 antagonist] group, dobutamine + ICI118,551 [specific beta-2 antagonist] group). AFC was measured by the single-nuclide tracer technique. Alpha-rat epithelial sodium channel (alpha-rENaC), beta-rENaC and gamma-rENaC mRNA expressions were measured by RT-PCR.

Results

(1) AFC of the dobutamine group and dobutamine + atenolol group were 26.6 ± 1.6% and 25.0 ± 5.3%, respectively, which were significantly higher than the normal control group (21.0 ± 3.9%) and dobutamine + ICI 118,551 group (21.0 ± 4.8%) (P < 0.05). There was no significant difference of AFC between the dobutamine group and dobutamine + atenolol group (P > 0.05); and no significant difference of AFC between the normal control group and dobutamine + ICI 118,551 group (P > 0.05). (2) AFC of the amiloride group was 6.0 ± 2.8%, which was significantly lower than the normal control group (P < 0.05). (3) AFC of the dobutamine + amiloride group was 10.0 ± 2.3%, significantly higher than the amiloride group (P < 0.05). (4) Gamma-rENaC mRNA expression of the dobutamine group and dobutamine + atenolol group was 0.90 ± 0.19 and 0.90 ± 0.09, respectively, significantly higher than the normal control group (0.69 ± 0.09) and dobutamine + ICI 118,551 group (0.68 ± 0.06) (P < 0.05). There was no significant difference of gamma-rENaC mRNA expression between the dobutamine group and dobutamine + atenolol group; and no significant difference of gamma-rENaC mRNA expression between the normal control group and dobutamine + ICI 118,551 group (P < 0.05). There was no significant difference of alpha-rENaC and beta-rENaC mRNA expressions between each group (P > 0.05). (5) Gamma-rENaC mRNA expression of the dobutamine + amiloride group was 0.70 ± 0.14, significantly lower than the dobutamine group and dobutamine + atenolol group (P < 0.05).

Conclusion

The amiloride-sensitive NaC pathway was important for lung epithelium to actively transport alveolar fluid. The effect of beta-2 adrenergic stimulation may upregulate gamma-rENaC expression and also stimulate the amiloride-insensitive NaC pathway to improve AFC in rats.