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Abstract: PO2463

Apelin, a Novel Apelin Receptor Analog, Improves Endothelial Dysfunction in Uremic Rats with 5/6 Nephrectomy

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Koc, Mehmet, Marmara University Medical Faculty, Division of Nephrology, Istanbul, Turkey
  • Ozdemir, Zarife, Marmara University Medical Faculty, Department of Physiology, Istanbul, Turkey
  • Akcay, Seckin, Marmara University Medical Faculty, Division of Endocrinology, Istanbul, Turkey
  • Yegen, Berrak, Marmara University Medical Faculty, Department of Physiology, Istanbul, Turkey
  • Kurtel, Hizir, Marmara University Medical Faculty, Department of Physiology, Istanbul, Turkey
Background

Endothelial dysfunction (ED), characterized by a reduction in vasodilation as a response to endothelial stimuli, has been reported in patients at almost all stages of chronic kidney disease (CKD). Considering that apelin is a vasoactive molecule causing nitric oxide release from endothelial cells, we aimed to investigate the regulatory role of apelin receptor on CKD-induced ED.

Methods

Adult Sprague Dawley male rats were randomized into sham-operation or 5/6-nephrectomy (CKD) groups. CKD groups were treated subcutaneously with saline (S-CKD) or 100 µg/day (each) of apelin (A-CKD), ala-apelin (Ala-CKD) or apelin+ala-apelin (A+Ala-CKD) for eight weeks. Isolated aortas were mounted in organ baths and their vasorelaxatory responses to carbachol (CCh) and apelin were evaluated following pre-contraction with phenylephrine.

Results

Aortas of S-CKD group demonstrated an impaired CCh-induced relaxation as compared to sham group (P<0.05), while pre-incubation with L-NAME further inhibited CCh-induced vasorelaxation in both sham and S-CKD groups (P<0.05) (Fig A). In A-CKD group, CCh-relaxation response was significantly improved compared to S-CKD group, but L-NAME attenuated the improvement in relaxation (Fig B-C). When apelin was added to organ bath, despite that S-CKD group showed no relaxation, a dose-dependent relaxation was observed in sham group, which was abolished in the presence of L-NAME (Fig D). In A-CKD, Ala-CKD and A+Ala-CKD groups, the relaxation response to apelin was enhanced as compared to S-CKD, while L-NAME pre-incubation abolished the relaxation (Fig E-F).

Conclusion

Apelin, which directly relaxes aortic rings of intact rats in an endothelium-dependent manner, ameliorates CKD-induced endothelial dysfunction when given as a treatment. Moreover, this beneficial effect of apelin treatment on endothelial vasomotor function appears to act by the preserving the activity of nitric oxide-signaling pathway.

Funding

  • Government Support – Non-U.S.