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Overexpression of a HIF prolyl‐4‐hydroxylase Transgene in the Renal Medulla Increases the Salt Sensitivity of Arterial Blood Pressure
Author(s) -
Xia Min,
Wang Zhengchao,
Zhang Fan,
Li PinLan,
Li Ningjun
Publication year - 2009
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.23.1_supplement.1017.28
Subject(s) - renal medulla , kidney , medicine , endocrinology , excretion , blood pressure , chemistry , transgene , medulla , transfection , biology , biochemistry , gene
We have demonstrated that HIF prolyl‐4‐hydroxylase domain‐containing proteins (PHDs), a family of enzymes that promote HIF‐1α degradation, are abundantly present in the renal medulla and regulate sodium excretion through regulation of HIF‐1 α and its targeted genes, such as nitric oxide synthase, cyclooxygenase and heme oxygenase. The present study was designed to test the hypothesis that overexpression a PHD transgene in the renal medulla increases the salt sensitivity of blood pressure. Plasmids expressing PHD2, the predominant isoform of PHDs in the kidneys, were transfected into the renal medulla in uninephretomized rats. Three weeks after PHD2 transfection, the mRNA levels of PHD2 was increased by two folds in the renal medulla. Mean arterial pressure measured by a telemetry system was significantly raised in PHD2 transfected rats after high salt challenge compared with control animals (131.3 ± 6.7 vs. 110.7 ± 4.2 mmHg). There was no blood pressure change in PHD2 transfected rats that were maintained on the normal salt diet. Urinary sodium excretion in response to acute sodium loading or elevation of renal perfusion pressure were blunted by 30% and 50%, respectively, in PHD2 transfected animals. In conclusion, PHD2 in the renal medulla importantly participates in the regulation of renal medullary function and in the long‐term control of arterial blood pressure. (Supported by NIH grant DK54927 and HL89563)