Modification of tubuloglomerular feedback signal by dietary protein

Abstract

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.

Effect of dietary protein on rat renin and angiotensinogen gene expression.

“…Prostaglandins are known to mediate renin release and may therefore be involved in the dietary protein induced changes in renin (24). High protein diets also result in increased loop of Henle sodium reabsorption and hence decreased sodium delivery to the macula densa, an effect that would also be expected to stimulate renin release (25).…”

Urea and Renal Function in the 21st Century

“…Microperfusion studies by Seney et al (68) determined that protein-induced increases in GFR result from changes in the tubuloglomerular feedback (TGF) system. Their studies found that the sensing mechanism of the TGF system was rendered less responsive by high protein intake and that the diminished TGF was caused, at least in part, by a reduced early distal NaCl concentration, without a change in early distal tubule osmolality (69).…”

Renal Phenotype of UT-A Urea Transporter Knockout Mice

“…Studies by Seney and Wright determined that this increase in GFR results from changes in the tubuloglomerular feedback (TGF) system (17,18). Furthermore, they determined that it is not an actual change in the sensing mechanism of the TGF response that is affected by high-protein diet, but rather it is an effect on the signal causing the TGF response.…”