Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency

International Journal of Molecular Sciences

Ilkka Pörsti¹  Onni Niemelä¹  Arttu Eräranta¹  Peeter Kööbi¹  Jukka Mustonen¹  Suvi Törmänen¹  Päivi Lakkisto²  Ilkka Tikkanen² 

[1] Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland;Minerva Institute for Medical Research, 00290 Helsinki, Finland;

关键词: chronic renal insufficiency;    chronic kidney disease;    endothelin receptor a;    endothelin receptor b;    creatinine;    calcium;    phosphate;    uric acid;    sitaxentan;    cinacalcet;    paricalcitol;   

DOI  :  10.3390/ijms21030936

来源: DOAJ

【 摘 要 】

Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine diet, representing proteinuric and interstitial inflammation models of CRI, respectively. Uric acid and calcium-phosphate metabolism were modulated after 5/6 nephrectomy, while ETA blocker and calcimimetic were given with adenine. Endothelin receptor mRNA levels were measured using RT-qPCR and protein levels using autoradiography (5/6 nephrectomy) or ELISA (adenine model). Both 12 and 27 weeks after 5/6 nephrectomy, kidney cortex ETA protein was increased by ~60% without changes in ETB protein, and the ETB:ETA ratio was reduced. However, the ETB:ETA mRNA ratio did not change. In the adenine model, kidney ETA protein was reduced by ~70%, while ETB protein was suppressed by ~95%, and the ETB:ETA ratio was reduced by ~85%, both at the protein and mRNA levels. The additional interventions did not influence the observed reductions in the ETB:ETA ratio. To conclude, unfavorable reduction in the ETB:ETA protein ratio was observed in two different models of CRI. Therefore, ETA blockade may be beneficial in a range of diseases that cause impaired kidney function.

【 授权许可】

Unknown