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Silencing of HIF prolyl-hydroxylase 2 gene in the renal medulla attenuates salt-sensitive hypertension in Dahl S rats.

Am J Hypertens. 2014; 
Zhu Q, Hu J, Han WQ, Zhang F, Li PL, Wang Z, Li N.
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摘要

In response to high salt intake, transcription factor hypoxia-inducible factor (HIF) 1α activates many antihypertensive genes, such as heme oxygenase 1 (HO-1) 1 and cyclooxygenase 2 (COX-2) in the renal medulla, which is an important molecular adaptation to promote extra sodium excretion. We recently showed that high salt inhibited the expression of HIF prolyl-hydroxylase 2 (PHD2), an enzyme that promotes the degradation of HIF-1α, thereby upregulating HIF-1α, and that high salt-induced inhibition in PHD2 and subsequent activation of HIF-1α in the renal medulla was blunted in Dahl salt-sensitive hypertensive rats. This study tested the hypothesis that silencing the PHD2 gene to increase HIF-1α levels in th... More

关键词

blood pressure; cyclooxygenase 2; heme oxygenase 1; hypertension; hypoxia-inducible factor; pressure natriuresis; sodium excretion.