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.
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