Dietary protein restriction improves the course of renal disease in the remnant kidney model. Dietary protein restriction can also reduce plasma renin activity in several circumstances. We examined the interaction between dietary protein and the renin-angiotensin system in subtotally nephrectomized rats (1-2/3 nephrectomy). No difference was seen in tissue renin activity in rats ingesting a high (30%) versus a low (6%) protein diet. To determine the pathophysiological role of angiotensin II in subtotally nephrectomized rats, we examined the acute renal response to an intrarenal infusion of the angiotensin II antagonist Sar1 Gly8-angiotensin II (10 μg/kg/min). Only those subtotally nephrectomized animals ingesting a high protein diet exhibited a consistent improvement in glomerular permselectivity, as manifested by a 24% fall in the fractional clearance of albumin (basal 16.19 ± 3.65 × 10-4 vs. Sar1 Gly8-AII 12.26 ± 3.21 × 10-4; P < 0.02) and a 19% fall in the fractional clearance of IgG (basal 3.75 ± 0.67 × 10-4 vs. Sar1 Gly8-AII 3.03 ± 0.48 × 10-4; P < 0.02). No consistent change occurred in glomerular permselectivity in the rats on the low protein diet or rats infused with vehicle only. No change in mean arterial pressure or whole-kidney hemodynamics were seen with angiotensin II blockade. Decrements in SNGFR and glomerular capillary pressure occurred with angiotensin blockade in the animals ingesting the high protein diet, suggesting hemodynamic factors as a mechanism for the improvement in permselective defects. In conclusion, dietary protein intake determines the glomerular response to angiotensin II blockade, implicating local angiotensin II as an injurious factor with high protein feeding in subtotally nephrectomized rats.
Bibliographical noteFunding Information:
Portions of this study were presented at the 1987 annual meeting of the American Society of Nephrology and were published in abstract form (Kidney mt 33:383, 1988) and at the November 1987 meeting of the Midwest Section of the American Federation for Clinical Research (Gun Res 35:871A, 1987). This work was supported by a U.S. Public Health Service Grant (AM 31437). M.E. Rosenberg was supported by a Research Fellowship from the Medical Research Council of Canada. We thank D. Chmielewski for his technical assistance and R. Suek for preparation of the manuscript.
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