Dataset Information

Collecting Duct Renin Does Not Mediate DOCA-Salt Hypertension or Renal Injury.

ABSTRACT: Collecting duct (CD)-derived renin is involved in the hypertensive response to chronic angiotensin-II (Ang-II) administration. However, whether CD renin is involved in Ang-II independent hypertension is currently unknown. To begin to examine this, 12 week old male and female CD-specific renin knock out (KO) mice and their littermate controls were subjected to uni-nephrectomy followed by 2 weeks of deoxycorticosterone acetate (DOCA) infusion combined with a high salt diet. Radiotelemetric blood pressure (BP) was similar between KO and control mice at baseline; BP increased in both groups to a similar degree throughout the 2 weeks of DOCA-salt treatment. Urinary albumin excretion and plasma blood urea nitrogen were comparable between the two groups after DOCA-salt treatment. Fibrosis as assessed by Masson's Trichrome stain/Sirius Red stain and collagen-1 mRNA expression was similar between control and KO mice. Compared to baseline, DOCA-salt treatment decreased plasma renin concentration (PRC), urinary renin excretion and medullary renin mRNA expression in both floxed and CD renin KO mice with no detectable differences between the two groups. Further, in primary culture of rat inner medullary CD, aldosterone treatment did not change renin activity or total renin content. Taken together, these data suggest that CD derived renin does not play a role in DOCA-salt hypertension.

SUBMITTER: Song K

PROVIDER: S-EPMC4965005 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Collecting Duct Renin Does Not Mediate DOCA-Salt Hypertension or Renal Injury.

Song Kai K Stuart Deborah D Abraham Nikita N Wang Fei F Wang Shuping S Yang Tianxin T Sigmund Curt D CD Kohan Donald E DE Ramkumar Nirupama N

PloS one 20160728 7

Collecting duct (CD)-derived renin is involved in the hypertensive response to chronic angiotensin-II (Ang-II) administration. However, whether CD renin is involved in Ang-II independent hypertension is currently unknown. To begin to examine this, 12 week old male and female CD-specific renin knock out (KO) mice and their littermate controls were subjected to uni-nephrectomy followed by 2 weeks of deoxycorticosterone acetate (DOCA) infusion combined with a high salt diet. Radiotelemetric blood p ...[more]

PMID: 27467376

Similar Datasets

Project description:BackgroundHigh salt intake is associated with both oxidative stress and chronic kidney disease (CKD) progression. Nuclear factor E2-related factor 2 (Nrf2) is a transcriptional factor regulating the antioxidant and detoxifying genes to potently antagonize oxidative stress. This study examined the effect of high salt loading on the expression of Nrf2 in kidney.MethodsMice were treated with acute salt loading, and Nrf2 expression in the kidney was detected by Western blotting and immunostaining. Reactive oxygen species (ROS) levels in the kidney were measured using dihydroethidium (DHE) staining. In vitro, mpkCCD cells were cultured in high osmolality medium by adding sodium chloride (NaCl), sodium gluconate (Na-Glu), choline chloride (Choline-Cl), or mannitol. Then, Nrf2 and its target genes were measured.ResultsNrf2 protein in renal cortex and medulla tissue lysates was significantly downregulated after acute salt loading. Immunofluorescence data showed that Nrf2 was mainly located in collecting duct principal cells evidenced by co-staining of Nrf2 with AQP2. Contrasting to the reduced Nrf2 expression, ROS levels in the kidney were significantly increased after salt loading. In vitro, the Nrf2 protein level was downregulated in mpkCCD cells after NaCl treatment for 24 h. Interestingly, sodium gluconate had a similar effect on downregulating Nrf2 expression as NaCl, whereas neither Choline-Cl nor mannitol changed Nrf2 expression. Meanwhile, the mRNA levels of Nrf2 target genes were downregulated by NaCl and/or sodium gluconate, while some of them were also regulated by Choline-Cl, indicating a more complex regulation of these genes under a high salt condition. Finally, we found that the downregulation of Nrf2 caused by NaCl was not affected by N-acetylcysteine (NAC), spironolactone, or NS-398, suggesting other mechanisms mediating Nrf2 downregulation caused by high salt challenge.ConclusionHigh salt downregulated Nrf2 mainly via a sodium-dependent manner in kidney collecting duct cells, which might contribute to the excessive renal oxidative stress and CKD progression.

Dataset Information

Collecting Duct Renin Does Not Mediate DOCA-Salt Hypertension or Renal Injury.

Publications

Collecting Duct Renin Does Not Mediate DOCA-Salt Hypertension or Renal Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets