This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Long-term consequences of high blood pressure including stroke, cardiorenal disease, and end-organ damage are, at least in part, due to a systemic and intrarenal activation of the renin angiotensin system. In contrast to the inhibitory effect that angiotensin II (Ang II) exerts on renin synthesized by juxtaglomerular cells, renin produced in distal Nephron segments is stimulated in Ang II-dependant hypertension. A pro-renin/renin receptor ?the (P)RR at the distal Nephron segments may represent a new generation of angiotensin peptides. Interaction of renin and (P)RR at the distal Nephron segments may represent a new paradigm to explain the increased intrarenal generation of angiotensin peptides and may also help to explain the activation of local signaling pathways contributing to renal injury and hypertension. However, the mechanisms involved in the regulation of distal Nephron renin, neither the contribution of its interaction with the (P)RR to the development and progression of the Ang II-dependant hypertension have been elucidated. This study will investigate the mechanisms responsible for the regulation of renin in the distal Nephron segments mediated by the chronic Ang II infusions and the implications of the interaction between renin and (P)RR during changes of dietary salt in Ang II-dependant hypertension by targeting the following specific aims: 1) To determine if chronically increased intrarenal Ang II content enhances renin production in the distal Nephron directly by activation of Ang II type 1 receptor or indirectly by stimulation of sodium Reabsorption via activation of amiloride-sensitive epithelial sodium channels and/or stimulation of aldosterone/specific mineralcorticoid receptors. 2) To determine the effects of changes in dietary salt on renin and the (P)RR in distal Nephron segments during Ang II-dependant hypertension;and 3) To determine whether chronic administration of the specific renin inhibitor Aliskiren, can attenuate the salt sensitivity hypertension and related intrarenal oxidative stress and kidney injury in chronic Ang II-infused rats by inhibition of renin and (P) RR in distal Nephron segments.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017659-10
Application #
8360257
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-07-01
Project End
2012-07-31
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
10
Fiscal Year
2011
Total Cost
$206,518
Indirect Cost
Name
Tulane University
Department
Physiology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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Hu, Tian; Yao, Lu; Reynolds, Kristi et al. (2016) Adherence to low-carbohydrate and low-fat diets in relation to weight loss and cardiovascular risk factors. Obes Sci Pract 2:24-31
Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng et al. (2015) Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension. Hypertension 65:352-61
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Gonzalez, Alexis A; Prieto, Minolfa C (2015) Renin and the (pro)renin receptor in the renal collecting duct: Role in the pathogenesis of hypertension. Clin Exp Pharmacol Physiol 42:14-21
Hu, Tian; Yao, Lu; Reynolds, Kristi et al. (2015) The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial. Nutrients 7:7978-94
Chen, Jing; Hamm, L Lee; Mohler, Emile R et al. (2015) Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease. PLoS One 10:e0132047
Rivara, Matthew B; Ikizler, T Alp; Ellis, Charles D et al. (2015) Association of plasma F2-isoprostanes and isofurans concentrations with erythropoiesis-stimulating agent resistance in maintenance hemodialysis patients. BMC Nephrol 16:79

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