Superoxide anion (02), is a product of cellular metabolism, generated due to partial reduction of molecular oxygen. As the presence of 02 can diminish the half life of nitric oxide (NO), the potential role of 02-NO interactions in the regulation of many biological events has been a major focus of many recent studies. Angiotensin II (ANG II) induces both 02 and NO production, indicating a possible role of NO-02 interaction in the pathophysiology of hypertension. Thus, the primary objectives of this project are to elucidate the interacting role of 02 and NO in the control of renal cortical and medullary circulation as well as tubular reabsorptive function. The hypothesis to be tested is that changes in intrarenal NO activity reciprocally regulate intrarenal 02 levels, which have a direct influence on renal hemodynamics and tubular function leading to alteraction in net sodium reabsorption rate. A deficiency in such regulation of NO and O2 may play a role in the development of ANG II dependent hypertension. Assessment of the interacting role of O2 and NO will be made in acute preparations in dogs as well as in chronic ANG II induced hypertensive rats. The effects of the administrations of tempol (a stable SOD mimetic) as well as a SOD inhibitor, Diethyldithiocarbamate on total and regional renal blood flows and excretory function will be assessed in the presence and absence of NO synthase inhibition. These assessments in renal regional hemodynamics will be made with the aid of single fiber laser Doppler needle flow probes in association with measurements of intrarenal NO activity using NO microelectrode and interstitial 8-isoprostanes level using microdialysis technique. It is anticipated that these experiments will provide a more complete understanding of the interactive role of 02 and NO in the regulation of renal cortical and medullary blood flows as well as excretory function both in under normal condition as well as in ANG II dependent hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066432-02
Application #
6537945
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Barouch, Winifred
Project Start
2001-07-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$222,750
Indirect Cost
Name
Tulane University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Singh, Purnima; Castillo, Alexander; Islam, M Toriqul et al. (2017) Evidence for Prohypertensive, Proinflammatory Effect of Interleukin-10 During Chronic High Salt Intake in the Condition of Elevated Angiotensin II Level. Hypertension 70:839-845
Mehaffey, Eamonn; Majid, Dewan S A (2017) Tumor necrosis factor-?, kidney function, and hypertension. Am J Physiol Renal Physiol 313:F1005-F1008
Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala et al. (2017) 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice. Hypertension 69:1104-1112
Maiti, Arpan K; Islam, Mohammed T; Satou, Ryousuke et al. (2016) Enhancement in cellular Na+K+ATPase activity by low doses of peroxynitrite in mouse renal tissue and in cultured HK2 cells. Physiol Rep 4:
Pingili, Ajeeth K; Thirunavukkarasu, Shyamala; Kara, Mehmet et al. (2016) 6?-Hydroxytestosterone, a Cytochrome P450 1B1-Testosterone-Metabolite, Mediates Angiotensin II-Induced Renal Dysfunction in Male Mice. Hypertension 67:916-26
Majid, Dewan S A; Prieto, Minolfa C; Navar, Luis Gabriel (2015) Salt-Sensitive Hypertension: Perspectives on Intrarenal Mechanisms. Curr Hypertens Rev 11:38-48
Whiting, Curtis; Castillo, Alexander; Haque, Mohammed Z et al. (2013) Protective role of the endothelial isoform of nitric oxide synthase in ANG II-induced inflammatory responses in the kidney. Am J Physiol Renal Physiol 305:F1031-41
Castillo, Alexander; Islam, M Toriqul; Prieto, Minolfa C et al. (2012) Tumor necrosis factor-ýý receptor type 1, not type 2, mediates its acute responses in the kidney. Am J Physiol Renal Physiol 302:F1650-7
Roy, Alexander; Khan, Abdul H; Islam, Mohammed T et al. (2012) Interdependency of cystathione ?-lyase and cystathione ?-synthase in hydrogen sulfide-induced blood pressure regulation in rats. Am J Hypertens 25:74-81
Lara, Lucienne S; McCormack, Michael; Semprum-Prieto, Laura C et al. (2012) AT1 receptor-mediated augmentation of angiotensinogen, oxidative stress, and inflammation in ANG II-salt hypertension. Am J Physiol Renal Physiol 302:F85-94

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