Abstract

This a competitive proposal that is based on two sets of preliminary data. In the first the PI has shown that cultured adrenocortical cells release into the supernatant one or more ouabain-like inhibitors of the Na, K pump. In the second, the PI has developed an HPLC-assisted quantitive reverse transcription-polymerase chain reaction (QRTPCR) method to quantitate mRNA levels in small amounts of tissue. Based on these, he is proposing two aims.
Aim 1 is to utilize several modern analytical techniques to characterize the inhibitor (s) of the Na, K pump released by adrenal Y1 cells. This will done via preliminary HPLC purification of relatively large amounts of supernatant medium which will be followed by tandem mass spectrometry and if the material reaches sufficient purity, by high resolution NMR. Selected chemical modifications of high purity material may also be used to aid in identification of the aforementioned inhibitor.
Aim 2 is to quantitate the levels of mRNA via the aforementioned QRTPCR method in defined segments of the rat nephron under different levels of dietary sodium intake.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK045538-07S1
Application #
6022105
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Akolkar, Beena
Project Start
1999-03-15
Project End
2000-08-14
Budget Start
1999-03-15
Budget End
2000-08-14
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225

  Publications

Dmitrieva, Renata I; Hinojos, Cruz A; Grove, Megan L et al. (2009) Genome-wide identification of allelic expression in hypertensive rats. Circ Cardiovasc Genet 2:106-15
Dmitrieva, Renata I; Hinojos, Cruz A; Boerwinkle, Eric et al. (2008) Hepatocyte nuclear factor 1 and hypertensive nephropathy. Hypertension 51:1583-9
Dmitrieva, Renata I; Lalli, Enzo; Doris, Peter A (2005) Regulation of adrenocortical cardiotonic steroid production by dopamine and PKA signaling. Front Biosci 10:2489-95
Doris, Peter A; Fornage, Myriam (2005) The transcribed genome and the heritable basis of essential hypertension. Cardiovasc Toxicol 5:95-108
Hinojos, Cruz A; Boerwinkle, Eric; Fornage, Myriam et al. (2005) Combined genealogical, mapping, and expression approaches to identify spontaneously hypertensive rat hypertension candidate genes. Hypertension 45:698-704
Hinojos, Cruz A; Doris, Peter A (2004) Altered subcellular distribution of Na+,K+-ATPase in proximal tubules in young spontaneously hypertensive rats. Hypertension 44:95-100
Abramowitz, Joel; Dai, Cuiping; Hirschi, Karen K et al. (2003) Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation 108:3048-53
Dmitrieva, Renata I; Doris, Peter A (2003) Ouabain is a potent promoter of growth and activator of ERK1/2 in ouabain-resistant rat renal epithelial cells. J Biol Chem 278:28160-6
Fornage, Myriam; Hinojos, Cruz A; Nurowska, Barbara W et al. (2002) Polymorphism in soluble epoxide hydrolase and blood pressure in spontaneously hypertensive rats. Hypertension 40:485-90
Doris, Peter A (2002) Hypertension genetics, single nucleotide polymorphisms, and the common disease:common variant hypothesis. Hypertension 39:323-31

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