The kidneys appear to play a role in shifting N from ureogenesis to gln synthesis in metabolic acidosis. The mechanism(s) responsible for this shift as well as for maintenance of gln and glucose homeostasis during acidosis are the long-term goals of this study. Evidence supporting a N distribution shift comes from the partitioning of urinary N as well as hepatoportal concentration differences measured in situ. Thus in metabolic acidosis, induced by either NH(4)Cl of HCl, the per cent of urinary N (NH(4)+urea) excreted as NH(3) rises from 2-5 in controls to 25-36 in acidosis. Direct evidence for hepatic involvement in N partition comes from the fall in urea and rise inglutamine release in acidosis. A new methological approach, regional blood flows measured by the pulsed Doppler Effect will provide for the first time in rat quantitative estimates of organ extraction/production rates; this approach not only constitutes a tremendous cost savings over large animal studies but also may be adapted for chronic studies. From the perspective or interorgan control this N shift could be affected by either kidney/muscle or gut/liver interactions. Renal venous HH(3) release (increased in acidosis) could favor muscle gln production at the expense of ala thereby depriving liver of a ureogenic precursor (ala) while sustaining renal NH(3) synthesis (gln). Portal drained viscera NH(3) release, at the expense of ala, appears to supply in a feed-forward fashion N in a form preferentially converted to gln. The relative quantitative contributions of both can be assessed using blood flow (hind limb and hepatic) and (A-V) of the major N carriers, NH(3) gln, glu, ala and urea. Renal influence on N distribution is seen in bilateral ureteral ligated acidotic rats which shifts urinary NH(3) to the renal venous release. In this condition NH(3)-N is incorporated into gln (muscle) and subsequently transformed into ala (gut) and finally deposited into urea (liver). The role of NH3 as a precursor or as a possible metabolic regulator (proteolysis) will be sutdied using the stable isotope 15N and measuring the differential incorporation into gln and urea (arterial as well as muscle and hepatic sites); a comparison of glutamine carbon, 14C, and nitrogen, 15N, turnover rates should provide insight into recycling. Kidneys may influence both glutamine and glucose homeostasis via renal NH3 release.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM021026-06
Application #
3151341
Study Section
General Medicine B Study Section (GMB)
Project Start
1978-01-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Louisiana State University Hsc Shreveport
Department
Type
Schools of Medicine
DUNS #
City
Shreveport
State
LA
Country
United States
Zip Code
71103