PMID- 31537914
OWN - NLM
STAT- MEDLINE
DCOM- 20201104
LR  - 20220420
IS  - 1348-4214 (Electronic)
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 42
IP  - 12
DP  - 2019 Dec
TI  - Effects of empagliflozin on nondiabetic salt-sensitive hypertension in 
      uninephrectomized rats.
PG  - 1905-1915
LID - 10.1038/s41440-019-0326-3 [doi]
AB  - Impaired pressure natriuresis (PN) underlies salt-sensitive hypertension, and 
      renal inflammation and hypoxia-inducible factor-1 (HIF-1) have been implicated in 
      the modulation of systemic hypertension. Although sodium-glucose cotransporter-2 
      (SGLT2) inhibitors were reported to lower blood pressure (BP) in type 2 diabetes 
      mellitus, whether they have a role in nondiabetic hypertensive kidney diseases is 
      unclear. The present study was undertaken to investigate whether nondiabetic 
      salt-sensitive hypertension and accompanying renal inflammation are ameliorated 
      by SGLT2 inhibition. Male Sprague-Dawley rats were randomly divided into three 
      groups: sham controls (SCs), uninephrectomized controls (UCs), and 
      empagliflozin-treated rats (ETs). All rats were fed a rodent diet with 8% NaCl 
      throughout the study period. Empagliflozin was orally administered for 3 weeks 
      after uninephrectomy. Systolic blood pressure was recorded weekly, and kidneys 
      were harvested for immunoblotting, immunohistochemistry, and quantitative PCR 
      analysis at the end of the animal experiment. Systolic BP was significantly 
      decreased in ETs that were orally given empagliflozin for 3 weeks after 
      uninephrectomy. Although ETs did not show any increase in weekly measured urine 
      sodium, the right-shifted PN relationship in UCs was improved by empagliflozin 
      treatment. The expression of HIF-1alpha was increased in the renal outer medulla of 
      ETs. Consistent with this, HIF prolyl-hydroxylase-2 protein and mRNA were 
      decreased in ETs. The abundance of CD3 and ED-1 immunostaining in UCs was reduced 
      by empagliflozin treatment. The increased IL-1ss, gp91phox, and NOX4 mRNA levels 
      in UCs were also reversed. Empagliflozin restored impaired PN in nondiabetic 
      hypertensive kidney disease in association with increased renal medullary 
      expression of HIF-1alpha and amelioration of renal inflammation.
FAU - Kim, Sua
AU  - Kim S
AD  - Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, 
      Korea.
FAU - Jo, Chor Ho
AU  - Jo CH
AD  - Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, 
      Korea.
FAU - Kim, Gheun-Ho
AU  - Kim GH
AD  - Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, 
      Korea. kimgh@hanyang.ac.kr.
AD  - Department of Internal Medicine, Hanyang University College of Medicine, Seoul, 
      Korea. kimgh@hanyang.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190919
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Slc5a2 protein, rat)
RN  - 0 (Sodium, Dietary)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*therapeutic use
MH  - Benzhydryl Compounds/*therapeutic use
MH  - Blood Pressure/drug effects
MH  - Glucosides/*therapeutic use
MH  - Hypertension, Renal/*drug therapy/physiopathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Male
MH  - Natriuresis/drug effects
MH  - Nephrectomy
MH  - Nephritis/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sodium, Dietary
MH  - Sodium-Glucose Transporter 2/drug effects
PMC - PMC8075936
OTO - NOTNLM
OT  - Empagliflozin
OT  - Hypoxia-inducible factor-1
OT  - Inflammation
OT  - Salt-sensitive hypertension
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/09/21 06:00
MHDA- 2020/11/05 06:00
PMCR- 2019/09/19
CRDT- 2019/09/21 06:00
PHST- 2019/05/03 00:00 [received]
PHST- 2019/08/22 00:00 [accepted]
PHST- 2019/08/08 00:00 [revised]
PHST- 2019/09/21 06:00 [pubmed]
PHST- 2020/11/05 06:00 [medline]
PHST- 2019/09/21 06:00 [entrez]
PHST- 2019/09/19 00:00 [pmc-release]
AID - 10.1038/s41440-019-0326-3 [pii]
AID - 326 [pii]
AID - 10.1038/s41440-019-0326-3 [doi]
PST - ppublish
SO  - Hypertens Res. 2019 Dec;42(12):1905-1915. doi: 10.1038/s41440-019-0326-3. Epub 
      2019 Sep 19.