Protein malnutrition is a world wide problem. Malnutrition affects renal function, including reductions in renal plasma flow (RPF) and glomerular filtration rate (GFR). We have also found reduced peripheral renin (PRA) and aldosterone activity, resistance to the hypertensive effects of exogenous norepinephrine (NE) and increased sensitivity to the blood pressure-lowering effects of alpha blockade. The mechanisms involved in these changes remain largely unknown.
The specific aim of this proposal is to establish the role played by various hormones and substances in this condition. Our data indicate that reduced the production of vasodilator prostaglandins and, possibly, increased sensitivity to the vasoconstrictor effects of angiotensin II and norepinephrine may be partly responsible for the reduced RPF, GFR and PRA. Also, low protein feeding of rats led to a fall in immunoreactive parathyroid hormone (iPTH), that may have curtailed the fall in GFR. We propose experiments to systematically examine the role of renin, angiotensin prostaglandins, NE, atrial natriuretic factor (ANF), antidiuretic hormone (ADH), and PTH on systemic and renal hemodynamics. Experiments will be conducted in rats fed low protein (6% casein) for two or sixteen weeks compared to controls pair-fed isocaloric normal protein (23% casein) diet. Balance, clearance and micropuncture studies (Munich-Wistar) will be done in intact, diabetes insipidus (Brattleboro) and parathyroidectomized rats. In addition, experiments will be conducted in isolated glomeruli and juxtaglomerular (granular) cells to determine the role of cyclic nucleotides (AMP and GMP), prostaglandins and various pharmacological agents in renin release. Radiocalcium fluxes and pharmacological manipulation of intracellular Ca mobilization will be performed in these preparations to determine the role of Ca. These experiments should provide important information regarding the systemic and renal hemodynamic changes associated with experimental and, possibly, human protein deficiency.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK030201-06
Application #
3229332
Study Section
General Medicine B Study Section (GMB)
Project Start
1988-07-01
Project End
1992-06-30
Budget Start
1990-09-25
Budget End
1992-06-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Pimentel Jr, J L; Montero, A; Wang, S et al. (1995) Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction. Kidney Int 48:1247-53
Pimentel Jr, J L; Sundell, C L; Wang, S et al. (1995) Role of angiotensin II in the expression and regulation of transforming growth factor-beta in obstructive nephropathy. Kidney Int 48:1233-46
Wang, S; Murtagh Jr, J J; Luo, C et al. (1993) Internal cRNA standards for quantitative northern analysis. Biotechniques 14:935-42
Benabe, J E; Wang, S; Wilcox, J N et al. (1993) Modulation of ANG II receptor and its mRNA in normal rat by low-protein feeding. Am J Physiol 265:F660-9
Martinez-Maldonado, M; Benabe, J E; Wilcox, J N et al. (1993) Renal renin, angiotensinogen, and ANG I-converting-enzyme gene expression: influence of dietary protein. Am J Physiol 264:F981-8
Pimentel Jr, J L; Martinez-Maldonado, M; Wilcox, J N et al. (1993) Regulation of renin-angiotensin system in unilateral ureteral obstruction. Kidney Int 44:390-400
Martinez-Maldonado, M; Delafontaine, P; Anwar, A et al. (1993) Aortic and renal regulation of the renin-angiotensin system in interrenal aortic coarctation. Trans Assoc Am Physicians 106:120-7
Benabe, J E; Pedraza-Chaverri, J; Martinez-Maldonado, M (1993) Mechanisms of ozolinone-induced renin release and diuresis. Am J Hypertens 6:701-7
Mendez, R E; Lopez, R; Lopez, G et al. (1991) Effects of dopamine-receptor antagonists and renal denervation on amino acid-induced hyperfiltration. Am J Physiol 261:F70-5