To examine angiotensin (ANG) concentrations in fluid compartments near known intrarenal ANG receptors, we measured ANG concentrations in glomerular filtrate (GF), star vessel plasma (SVP), and luminal fluid from the early, mid, and late proximal tubule (E, M, and L PT). Samples were collected from euvolemic Munich-Wistar rats by free-flow micropuncture; ANG concentrations were measured by RIA. In one group of rats, concentrations of total immunoreactive ANG (reflecting ANG II and lesser amounts of three fragments) in GF and E, M, and L PT fluid averaged 29-40 nM compared with 32 pM in systemic plasma. In a second group, immunoreactive ANG concentrations in SVP also exceeded systemic levels by a factor of 1,000. In a. final group, samples of GF and LPT fluid were purified by HPLC before RIA to measure ANG II and III concentrations specifically: their respective concentrations were 6-8 nM and 14-25 nM. We interpret these results to indicate that substantial amounts of ANG peptides are released into or generated within intrarenal fluid compartments, in which local ANG is likely to effect regulation of renal function independently of systemic ANG. (J. Clin. Invest. 1990.

Compared with the effects of a 6% protein diet, feeding rats a 40% protein diet for 10 days increases glomerular filtration rate and decreases the activity of the tubuloglomerular (TG) feedback control system. The decrease in TG feedback activity results from an increase in the threshold at which the loop of Henle flow rate initiates feedback responses. To determine whether this protein-dependent shift in the TG feedback response curve is caused by changes in either the signal or the sensing mechanism in the feedback pathway, we used micropuncture and microperfusion techniques to study the TG feedback system of rats fed high- or low-protein (40 or 6% casein) diets for approximately 7-10 days. Compared with the rats fed the low-protein diet, in the high-protein group distally measured single nephron glomerular filtration rate was 17% higher, and Na and Cl concentrations in early distal tubule fluid were 30-50% lower. Early distal osmolality was not different in the two groups. TG feedback responses assessed by changes in stop-flow pressure during perfusion of the distal nephron with NaCl solutions did not differ between diet groups. We conclude that the sensing mechanism in the TG feedback system is not altered by this manipulation of dietary protein, whereas the signal eliciting the TG feedback response is affected. Because rats fed a high-protein diet have higher rates of Na and Cl absorption between the late proximal and early distal tubules than do rats fed a low-protein diet, early distal Na and Cl concentrations are reduced, and the signal for TG feedback is diminished in rats fed the high-protein diet.

No abstract

We have examined the possibility that changes in glomerular filtration rate (GFR) after changes in dietary protein intake may depend on altered function of the tubuloglomerular (TG) feedback system. We studied male Sprague-Dawley rats after dietary pretreatment for 9.6±3.6 (SD) d with isocaloric diets containing either 6% or 40% casein. We found that GFR in rats fed the high protein diet was 24-29% higher than in rats fed the low protein diet. Simultaneous measurements of single nephron GFR (SNGFR) in the distal tubule were 6.3 nl/min or 21% higher in the rats fed the high protein diet whereas proximally measured SNGFR was not statistically different in the two groups. The higher distally measured SNGFR of rats receiving the high protein diet was associated with a 4.2 nI/ min or 50% smaller suppression of SNGFR by TG feedback (-4.3 vs. -8.5 nl/min, P < 0.001). Loop perfusion experiments demonstrated that in rats fed the high protein diet the TG feedback mechanism was less sensitive than in rats fed the low protein diet. The TG feedback response in rats fed the low protein diet, as assessed by reductions in stop-flow pressure and SNGFR, was half-maximal at flows of 14-15 nl/min. In contrast, the TG feedback response in rats fed the high protein diet was half-maximal at 22-24 nl/min. Maximal suppression of stop-flow pressure and SNGFR and the slope of the TG feedback response to increasing loop flow rates were not different in the two groups. We conclude that the sensing mechanism of the TG feedback system is rendered less responsive by a high protein intake, and that this change permits GFR to increase.