title: Overexpression of HIF-1α transgene in the renal medulla attenuated salt sensitive hypertension in Dahl S rats.
abstract: Hypoxia inducible factor (HIF)-1α-mediated gene activation in the renal medulla in response to high salt intake plays an important role in the control of salt sensitivity of blood pressure. High salt-induced activation of HIF-1α in the renal medulla is blunted in Dahl S rats. The present study determined whether the impairment of the renal medullary HIF-1α pathway was responsible for salt sensitive hypertension in Dahl S rats. Renal medullary HIF-1α levels were induced by either transfection of HIF-1α expression plasmid or chronic infusion of CoCl₂ into the renal medulla, which was accompanied by increased expressions of anti-hypertensive genes, cyclooxygenase-2 and heme oxygenase-1. Overexpression of HIF-1α transgenes in the renal medulla enhanced the pressure natriuresis, promoted the sodium excretion and reduced sodium retention after salt overload. As a result, hypertension induced by 2-week high salt was significantly attenuated in rats treated with HIF-1α plasmid or CoCl₂. These results suggest that an abnormal HIF-1α in the renal medulla may represent a novel mechanism mediating salt-sensitive hypertension in Dahl S rats and that induction of HIF-1α levels in the renal medulla could be a therapeutic approach for the treatment of salt-sensitive hypertension.
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richnond VA 23298, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Pin-Lan
authors.initials: PL
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Ningjun
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003035:Cobalt / Q000494:pharmacology / Q000652:urine; D051546:Cyclooxygenase 2 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009318:Natriuresis; D051381:Rats; D020303:Rats, Inbred Dahl; D015533:Transcriptional Activation
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C018021:cobaltous chloride