Chronic salt loading: effects on plasma volume and regulation of glomerular filtration rate in Wistar rats

Experiments were carried out in Wistar rats to determine whether the loss of sensitivity of the tubuloglomerular feedback mechanism (TGF) which is known to occur in volume expansion is due to a change in the functional characteristics of the juxtaglomerular apparatus or to a change in some property of the tubular fluid which influences the feedback signal at the macula densa. Proximal tubular fluid was collected by means of a microperfusion/suction pump from Wistar rats maintained for a minimum of 10 days on a high salt diet and also from rats fed a control low salt diet. Both fluids were then used to perfuse loops of Henle in rats from both groups and the feedback response assessed from the change in early proximal tubular flow rate (EPF). In high salt rats, perfusion of the loop of Henle with homologous tubular fluid confirmed the loss of sensitivity of the TGF mechanism in volume expansion, the response of EPF was practically absent. In contrast, the low salt rat responded with a 50% decrease in EPF to loop perfusion at 40 nl/min with its homologous fluid. On the other hand, when the loop of Henle in high salt rats was perfused at 40 nl/min with heterologous (low salt) tubular fluid, EPF again decreased by some 50% whereas EPF in low salt rats failed to respond to loop perfusion with high salt fluid. From these results it is concluded that in rats chronically volume expanded by a high salt diet an unknown inhibitory principle occurs in the proximal tubular fluid which reduces the sensitivity of the tubuloglomerular feedback mechanism.