The proximal tubule (PT) can synthesize and secrete endogenous angiotensin II into the lumen. We have demonstrated that endogenous angiotensin II can modulate PT transport (Quan A, Baum M. J Clin Invest 1996. 97: 2878-2882). Luminal administration of Dup 753 (angiotensin receptor antagonist) or of enalaprilat (converting enzyme inhibitor) decreased PT volume reabsorption by 35 - 40%. These data are consistent with stimulation of PT transport by endogenously produced angiotensin II. In this study, we examined if endogenously produced and luminally secreted angiotensin II is regulated by acute changes in extracellular volume.

The effect of luminal perfusion of Dup 753 on the PT volume reabsorptive rate was measured via in vivo microperfusion between oil blocks. The reduction in volume reabsorption after addition of luminal Dup 753 is a measure of how endogenously produced and luminally secreted angiotensin II affects PT transport. During hydropenia, luminal perfusion of 10^(-8) M Dup 753 decreased volume reabsorption by 58.0±7.0% (1.70±0.30 vs. 4.20±0.50 nl/min·mm, p≤0.05). In contrast, after acute volume expansion, luminal perfusion of 10^(-8) M Dup 753 decreased volume reabsorption by only 29.6±9.0% (1.31±0.20 vs. 1.84±0.20 nl/min·mm, p≤0.05). The percent decrease in the volume reabsorption observed with perfusion of Dup 753 during hydropenia was significantly greater than that in the volume expanded state, p≤0.05. In hydropenic rats, addition of 10^(-8)M angiotensin II to the luminal perfusate had no effect on volume reabsorption because of the high rate of endogenous production. In volume expanded rats, addition of 10^(-8)M angiotensin II increased volume reabsorption from 2.10±0.34 to 4.38±0.59 nl/min·mm, p≤0.005.

These data support an autocrine/paracrine role for angiotensin II, where endogenously produced and luminally secreted angiotensin II augments PT transport to a proportionately greater degree during hydropenia than after volume expansion.