Abstract

Because of the countercurrent arrangement of blood flow in the capillaries of the renal medulla, medullary tension is always low, and medullary cells, especially of the thick ascending limb (mTAL), are at special risk of hypoxic injury. We hypothesize that local mechanisms normally operate to feedback and down-regulate transport activity in these cells, in order to protect them from anoxic damage. We therefore intend to investigate autocrine and paracrine substances that may modulate transport of the mTAL. These include adenosine, prostaglandin E2, and other eicosanoids. The effects of these substances on respiration and transport by mTAL tubules and cells, their mechanism of action, and their local production and action in states of increased cellular transport or of hypoxia will be examined. As a counterpoint to these studies, we will investigate the effect of prostaglandins on another species of medullary tubule, the inner medullary collecting duct.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK018078-20S1
Application #
2137154
Study Section
General Medicine B Study Section (GMB)
Project Start
1974-09-01
Project End
2000-03-31
Budget Start
1993-04-01
Budget End
2000-03-31
Support Year
20
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Prasad, P V; Priatna, A; Spokes, K et al. (2001) Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model for radiocontrast nephropathy. J Magn Reson Imaging 13:744-7
Priatna, A; Epstein, F H; Spokes, K et al. (1999) Evaluation of changes in intrarenal oxygenation in rats using multiple gradient-recalled echo (mGRE) sequence. J Magn Reson Imaging 9:842-6
Silva, P; Solomon, R J; Epstein, F H (1999) Mode of activation of salt secretion by C-type natriuretic peptide in the shark rectal gland. Am J Physiol 277:R1725-32
Prasad, P V; Epstein, F H (1999) Changes in renal medullary pO2 during water diuresis as evaluated by blood oxygenation level-dependent magnetic resonance imaging: effects of aging and cyclooxygenase inhibition. Kidney Int 55:294-8
Epstein, F H (1997) Oxygen and renal metabolism. Kidney Int 51:381-5
Gunning, M; Solomon, R J; Epstein, F H et al. (1997) Role of guanylyl cyclase receptors for CNP in salt secretion by shark rectal gland. Am J Physiol 273:R1400-6
Greenfeld, Z; Stillman, I E; Brezis, M et al. (1997) Medullary injury in the ageing rat kidney: functional-morphometric correlations. Eur J Clin Invest 27:346-51
Mulkerrin, E C; Clark, B A; Epstein, F H (1997) Increased salt retention and hypertension from non-steroidal agents in the elderly. QJM 90:411-5
Derman, M P; Chen, J Y; Spokes, K C et al. (1996) An 11-amino acid sequence from c-met initiates epithelial chemotaxis via phosphatidylinositol 3-kinase and phospholipase C. J Biol Chem 271:4251-5
Medina, R; Cantley, L; Spokes, K et al. (1996) Effect of water diuresis and water restriction on expression of HSPs-27, -60 and -70 in rat kidney. Kidney Int 50:1191-4

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