Regulation of renal proximal fluid uptake by luminal and peritubular angiotensin II.

INTRODUCTION: Angiotensin II (Ang II), when administered to either tubular lumen or peritubular capillary, exerts a biphasic action on proximal fluid uptake rate. At low concentrations, (10(-12)-10(-10) M) Ang II stimulates fluid transport, whereas higher doses (>10(-9) M) inhibit. Ang II is secreted into the lumen in the proximal tubule and the concentration of Ang II in the proximal lumen has been reported to be in the nanomolar range, 100-1,000 times higher than in peritubular blood. We investigated the regulation of renal proximal fluid transport by luminal (predominantly locally produced) and peritubular capillary (circulatory) Ang II in anaesthetised rats, using a selective AT(1)-receptor antagonist, candesartan. METHODS: Experiments were performed in inactin-anaesthetised male Wistar rats. Proximal fluid uptake rate was measured using computerised capture and analysis of shrinking-split droplet microperfusion in response to either luminal addition or luminal addition with simultaneously peritubular capillary perfusion of 10(-8) M candesartan. RESULTS: Luminal addition of candesartan (10(-8) M) decreased fluid absorption by 19-25%. Perfusion of the peritubular capillaries with an electrolyte solution (containing no Ang II) reduced fluid uptake by 27%, and blockade of the peritubular actions of Ang II by addition of candesartan (10(-8) M) resulted in 33% decrease in fluid uptake. However, when candesartan (10(-8) M) was added to both luminal and capillary perfusates, there was a 43% reduction in fluid transport when compared with initial values. CONCLUSION: These results suggest that the presence of endogenous Ang II in both peritubular blood and luminal fluid is important for maximal expression of the stimulatory influence of this peptide on proximal tubule fluid uptake.