Doxazosin attenuates renal matrix remodeling mediated by anti-α(1)-adrenergic receptor antibody in a rat model of diabetes mellitus

Diabetic nephropathy is a major complication of diabetes mellitus (DM). Recent studies suggest that immunological mechanisms have a key role in the pathogenesis of DM, therefore these mechanisms may be important targets for diabetes therapy. The present study evaluated the effects of anti-α(1)-adrenergic receptor antibody (α(1)-R Ab) mediation and doxazosin treatment in a rat model of DM. It was observed that levels of 24-h urinary protein, serum creatinine and transforming growth factor-β(1) in DM were significantly increased after α(1)-R Ab mediation (all P<0.05). In addition, electron microscopy identified severe damage in the renal tissue microstructures of DM rats following α(1)-R Ab mediation, while only mild abnormalities were observed in that of healthy rats mediated with α(1)-R Ab and of untreated DM rats. No marked abnormalities were observed in the renal tissue of healthy blank controls. Furthermore, in DM rats treated with α(1)-R Ab mediation + doxazosin intervention, the expression of TGF-β(1) significantly decreased, and renal functions and renal matrix remodeling were significantly improved, relative to untreated DM controls (P<0.01). These results suggest that α(1)-R Ab may be involved in renal matrix remodeling during DM, and that kidney protection during DM may be achieved through treatment with corresponding receptor antagonists.