Abstract

The overall goal of the proposed studies is to determine the cellular and molecular mechanisms surrounding the interaction between the NOS and ET pathways in the inner medulla of the kidney in response to high salt. We predict that the intrarenal production of ET in response to high salt intake activates the abundant ETB receptors in the inner medulla. Our hypothesis predicts that activation of the ETB receptors in the renal inner medulla will result in a stimulation of NOS and subsequent production of NO which in turn inhibits Na reabsorption. These mechanisms contribute to the kidney's ability to control sodium excretion, and therefore, play an important role in fluid-volume regulation and the control of blood pressure.
Specific Aim 1. To test the hypothesis that ETB receptor stimulation inhibits Na transport via NO production in renal inner medullary collecting duct cells.
Specific Aim 2. To test the hypothesis that ETB receptor stimulation increases Na excretion via NOS 1-mediated NO production in the renal inner medulla.
Specific Aim 3. To test the hypothesis that the mechanism of NOS 1-mediated NO production in the renal inner medulla is through NOS 1 dephosphorylation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL060653-05
Application #
6681977
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Barouch, Winifred
Project Start
1998-07-01
Project End
2007-06-30
Budget Start
2003-07-10
Budget End
2004-06-30
Support Year
5
Fiscal Year
2003
Total Cost
$275,250
Indirect Cost

  Institution

Name
Medical College of Georgia (MCG)
Department
Pharmacology
Type
Schools of Medicine
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912

  Publications

Spradley, Frank T; Ho, Dao H; Pollock, Jennifer S (2016) Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium. Am J Physiol Regul Integr Comp Physiol 310:R286-96
Hyndman, Kelly A; Xue, Jing; MacDonell, Alexander et al. (2013) Distinct regulation of inner medullary collecting duct nitric oxide production from mice and rats. Clin Exp Pharmacol Physiol 40:233-9
Spradley, F T; Kang, K-T; Pollock, J S (2013) Short-term hypercaloric diet induces blunted aortic vasoconstriction and enhanced vasorelaxation via increased nitric oxide synthase 3 activity and expression in Dahl salt-sensitive rats. Acta Physiol (Oxf) 207:358-68
Hyndman, Kelly A; Pollock, Jennifer S (2013) Nitric oxide and the A and B of endothelin of sodium homeostasis. Curr Opin Nephrol Hypertens 22:26-31
De Miguel, C; Foster, J M; Carmines, P K et al. (2013) Interaction between NO synthase and NADPH oxidase in control of sodium transport by the renal thick ascending limb during diabetes. Acta Physiol (Oxf) 209:148-55
Spradley, Frank T; De Miguel, Carmen; Hobbs, Janet et al. (2013) Mycophenolate mofetil prevents high-fat diet-induced hypertension and renal glomerular injury in Dahl SS rats. Physiol Rep 1:e00137
Spradley, Frank T; White, John J; Paulson, William D et al. (2013) Differential regulation of nitric oxide synthase function in aorta and tail artery from 5/6 nephrectomized rats. Physiol Rep 1:e00145
Hyndman, Kelly A; Boesen, Erika I; Elmarakby, Ahmed A et al. (2013) Renal collecting duct NOS1 maintains fluid-electrolyte homeostasis and blood pressure. Hypertension 62:91-8
Hyndman, Kelly A; MacDonell, Alexander H; Pollock, Jennifer S (2012) Extracellular signal-regulated kinases 1/2 signaling pathways are not involved in endothelin regulation of mouse inner medullary collecting duct nitric oxide production. Life Sci 91:578-82
Kittikulsuth, Wararat; Pollock, Jennifer S; Pollock, David M (2012) Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II. Am J Physiol Renal Physiol 303:F659-66

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