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논문분류	춘계학술대회 초록집
제목	Antihypertensive effect of empagliflozin in salt-loaded uninephrectomized rat
저자	Sua Kim, Chor Ho Jo, Gheun-Ho Kim
출판정보	2018; 2018(1):
키워드	NaCl \| SGLT2 \| hypertension \| inflammation \| hypoxia-inducible factor-1
초록	Objectives: Although sodium-glucose cotransporter-2 (SGLT2) inhibitors were reported to exert blood pressure lowering in type 2 diabetes mellitus, whether they have a role in non-diabetic hypertensive kidney diseases is not clear. This study was undertaken to investigate whether salt-sensitive hypertension and its accompanying renal inflammation are ameliorated by SGLT2 inhibition. Methods: The animal model of salt-sensitive hypertension was established by salt loading in uninephrectomized rats. Male Sprague-Dawley rats were randomly divided into 3 groups: sham controls (SC, n=4), uninephrectomized controls (UC, n=4), and empagliflozin-treated rats (ET, n=5). All rats were fed a rodent diet with 8% NaCl throughout the study period. Empagliflozin (20 mg/kg/d) was orally administered for 3 weeks after uninephrectomized rats were stabilized over 2 weeks. Results: At the end of animal experiment, SBP in UC was higher than that in SC (168 ± 2 vs. 138 ± 3 mmHg, P<0.01). Compared with UC, however, ET had a lower SBP (146 ± 1 mmHg, P<0.05). Glycosuria was remarkable in ET, and urinary excretion of osmoles in ET was significantly increased. Compared with SC and UC, the abundance of HIF-1α protein in renal medulla was increased in ET (262 ± 83%, P<0.05). Compared with SC, the mRNA expression levels of IL-1b (268 ± 46%, P<0.05), RANTES (167 ± 10%, P<0.05), and gp91phox (300 ± 18%, P<0.05) were increased in UC but ameliorated in ET (IL-1b, 159 ± 13%; RANTES, 87 ± 15%; gp91phox, 142 ± 33%, all P<0.05). Conclusions: Empagliflozin was effective in controlling salt-sensitive hypertension induced by renal mass reduction via glycosuria-driven osmotic diuresis. Besides, its antihypertensive effect was accompanied by increased renal medullary expression of HIF-1α and amelioration of renal inflammation.
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