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Inhibition of hypoxia inducible factor‐1α in the renal medulla contributes to fructose‐induced salt‐sensitive hypertension
Author(s) -
Hu Junping,
Zhu Qing,
Li PinLan,
Boini Krishna M.,
Li Ningjun
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1216.2
Subject(s) - fructose , medicine , endocrinology , chemistry , renal medulla , blood pressure , kidney , sodium , ingestion , biochemistry , biology , organic chemistry
Excessive fructose ingestion has been closely associated with hypertension and shown to increase the salt sensitivity of blood pressure. We have previously demonstrated that high salt‐induced activation of hypoxia inducible factor (HIF)‐1α in the renal medulla is an important adaptive mechanism to remove extra sodium load and maintain normal blood pressure in response to a high salt intake. The present study tested the hypothesis that dietary fructose inhibits high salt‐induced activation of HIF‐1α in the renal medulla and thereby increases salt‐sensitivity of blood pressure. Adult Sprague‐Dawley rats were divided into 4 groups: low salt diet (LS, 0.4%NaCl), high salt diet (HS, 8% NaCl), LS+fructose (20% in drinking water) and HS+fructose. After 10 day treatment, mean arterial pressure (MAP) was significantly higher in rats fed with HS+fructose than all other groups, whereas MAP was not different among groups of LS, HS and LS+fructose (MAP: 103 ± 4.7 mmHg in LS group, 104 ± 2.4 in LS+fructose, 105 ± 3.4 in HS, and 120 ± 2.03 in HS+fructose, P<0.05). Interestingly, high salt‐induced increase of renal medullary HIF‐1α protein levels was significantly inhibited by fructose. The relative levels of HIF‐1α in the renal medulla in groups of LS, HS, LS+Fructose and HS+Fructose were 1 ± 0.10, 2.05 ± 0.36, 0.18 ± 0.008, 0.19 ± 0.05 (P<0.05), respectively. The mRNA levels of HIF‐1α target gene heme oxygenase (HO)‐1 was also inhibited by 69% in HS+Fructose group compared with HS group. Furthermore, overexpression HIF‐1α transgene in the renal medulla corrected the reduced levels of HIF‐1α and its target gene HO‐1 in the renal medulla and attenuated the increase of blood pressure induced by HS+fructose (MAP: 104 ± 3.9 mmHg in LS group, 107 ± 2.3 in LS+fructose, 107 ± 3.1 in HS, 124 ± 3.4 in HS+fructose, and 114 ± 1.4 in HS+fructose+HIF‐1α transgene, P<0.05). These results suggested that inhibition of HIF‐1α‐mediated gene activation in the renal medulla participates in the mechanisms of fructose‐induced salt‐dependent hypertension, and manipulating HIF‐1α signaling pathway may be used as a therapeutic strategy in fructose‐induced salt‐dependent hypertension. Support or Funding Information support: NIH grant: HL89563 and HL106042