S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Clinical Medical Sciences (임상의과학과) Theses (Ph.D. / Sc.D._임상의과학과)
Alterations of Renal Sodium Transporters in the Erythropoietin-treated Chronic Renal Failure Rat : 신부전 백서 모델에서 erythropoietin 투여에 따른 소디움 운반체 변화
- Jin Suk Han
- 의과대학 임상의과학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 임상의과학과, 2013. 2. 한진석.
- Introduction: Erythropoietin (EPO) administration in uremic rats leads to an increase in blood pressure. However, the adaptive mechanism of kidney and renal sodium transporters to EPO is not well explored. The present study was designed to investigate the change of sodium balance and alteration of major renal sodium transporters in erythropoietin (EPO)-treated chronic renal failure rat.
Methods: Renal failure was induced by a two-stage 5/6 nephrectomy in 30 Sprague-Dawley rats. Three weeks after the operation, uremic rats were divided into two groups and received vehicle and EPO (150 U/kg, intraperitoneal injection, two times per week) for 4 weeks. Half of the rats were sacrificed after 1 week of EPO administration, and the rest after 4 weeks.
Results: Serum creatinine and sodium level, hematocrit, body weight, and systolic blood pressure were similar in both groups before treatment. After 1 week of treatment, hematocrit increased in the EPO group (48.9 ± 0.8 vs. 38.4 ± 1.0%, P = 0.001). Systolic blood pressure (SBP) was 153.5 ± 6.8 mmHg in the EPO group and 147.3 ± 4.7 mmHg in control group (P = 0.793) after 1 week. After 4 weeks treatment, SBP increased significantly (159.5 ± 3.3 vs. 146.4 ± 2.3 mmHg, P = 0.007). Urinary sodium excretion and daily sodium balance did not show significant difference between groups throughout the experiment period. Expression of ENaC α decreased significantly (58.6 ± 5.1% of the control, P < 0.001) after 1 week of EPO treatment on immunoblot analysis. After 4 weeks of treatment, the renal abundances of ENaC α, γ, and NHE3 significantly decreased (56.1 ± 6.1%, 49.4 ± 9.7%, and 38.6 ± 9.4% of the control, P = 0.011, 0.026, and 0.007, respectively) in the EPO group. Renal medullary endothelin levels of EPO-treated group increased significantly (10.2 ± 2.9 pg/mg vs. 5.2 ± 0.8 pg/mg, P = 0.028, at the 1st week
3.6 ± 0.8 pg/mg vs. 1.5 ± 0.4 pg/mg, P = 0.035, at the 4th week) than that of control group. Plasma renin and serum aldosterone levels were not different between groups.
Conclusions: EPO increases renal medullary endothelin-1, and inhibits renal ENaC and NHE3 expression. Increased production of renal medullary endothelin-1 and decreased expression of renal sodium transporters might work as compensatory mechanisms in EPO-treated hypertensive chronic renal failure model.