DISTAL TUBULE [NA plus ] AND JUXTAGLOMERULAR APPARATUS RENIN-ACTIVITY IN URANYL-NITRATE INDUCED ACUTE RENAL-FAILURE IN RAT - EVALUATION OF ROLE OF TUBULOGLOMERULAR FEEDBACK

Single nephron filtration rate, whole kidney glomerular filtration rate and total renal blood flow decrease by 30-35% 6 h after uranyl nitrate induced acute renal failure in the rat. To evaluate a role of the renin-angiotensin system in the initiating phase (0-6 h) of this model of acute renal failure, determinations of plasma renin activity, superficial (S) and deep (D) juxtaglomerular apparatus (JGA) renin activity and distal nephron Na+ concentration [Na+] were obtained. Plasma renin activity increased from the control value of 1.5 .+-. 0.3 (standard error of the mean) to 2.9 .+-. 0.4 ng/ml per h (P < 0.005) at 6 h. Mean renin activity in S- and D-JGA''s of control rats was 6.99 .+-. 0.41 and 2.67 .+-. 0.21 ng/JGA per h, respectively. After uranyl nitrate, renin activity in S-JGA''s increased to 13.62 .+-. 0.80 ng/JGA per h (P < 0.001) at 2 h and remained elevated, 12.56 .+-. 0.90 and 12.75 .+-. 0.87 ng/JGA per h at 4 and 6 h. D-JGA renin activity increased (P < 0.05) to 7.04 .+-. 0.53, 6.23 .+-. 0.31 and 3.44 .+-. 0.33 ng/JGA per h at 2, 4 and 6 h after uranyl nitrate. Distal tubule [Na+], 27 samples in 6 rats, increased from a mean control value of 53.7 .+-. 1.2 meq/l to 116.9 .+-. 2.5 meq/l, 24 samples in 6 rats (P < 0.001). Prompt increases in JGA renin activity were observed in the initiating phase of acute renal failure, suggesting a role for the renin-angiotensin system in the pathophysiology of this nephrotoxic model. The association of increased JGA renin activity and increased distal [Na+] is consistent with a role for the tubuloglomerular feedback mechanism in the initiating phase of uranyl nitrate induced acute renal failure in the rat.