The physiologic importance of the renin-angiotensin system (RAS) in maintaining cardiovascular homeostasis is undisputed. Recent observations have expanded the traditional views of the morphology and function of renin-secreting cells. A) Two distinct renal cell types, epithelioid juxtaglomerular cells (JG cells) and distal afferent arteriolar smooth muscle cells, are known to contain and secrete renin. B) The renin angiotensin system has local and systemic actions in controlling cardiovascular homeostasis. C) Renin isoforms with differing metabolic half lives have been identified. The working hypothesis is that JG cells and distal afferent arteriolar cells contain and secrete different renin isoforms. Through these differences the two cell types may contribute in distinct ways to regulation of vascular homeostasis. The long term goal of this proposal is to define the secretory patterns and renin isoforms of unstimulated and stimulated renin release in rat kidney JG cells and distal afferent arteriolar cells. In this proposal, Dr. Norling will apply cell biology techniques of pulse chase analysis of secretion for studying renin secretion in two renin- containing cell types from rat kidney. Renin isoforms from these cells will be characterized and compared. From these experiments it is expected that Dr. Norling will find that JG cells and distal afferent arteriolar cells have renin processing capabilities which are cell-type specific. This information will help to expand the understanding of RAS regulation of vascular tone.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08DK002048-01A2
Application #
3080980
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1993-06-01
Project End
1998-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Norling, L L; Smith, T M; Ingelfinger, J R (1998) Stored renin isoforms in the developing rat kidney. Am J Hypertens 11:213-8
Norling, L L; Tufro-McReddie, A; Ariel Gomez, R et al. (1996) Accumulation of acidic renin isoforms in kidneys of cyclosporine-A-treated rats. J Am Soc Nephrol 7:331-7
Norling, L L; Gomez, R A; Inagami, T (1995) Characterization of a synthetic peptide antibody recognizing rat kidney renin and prorenin. Clin Nephrol 43:232-6