Effect of luminal angiotensin II receptor antagonists on proximal tubule transport

The proximal tubule can endogenously synthesize and secrete luminal angiote nsin II at a concentration approximately 100- to 1000-fold higher than that in the systemic circulation. We have recently shown that this endogenously produced and luminally secreted angiotensin II regulates proximal tubule v olume reabsorption, which is a reflection of sodium transport within this s egment. In this study, we use in vivo microperfusion of angiotensin II rece ptor antagonists into the lumen of the proximal tubule to examine the role of the luminal AT(1) and AT(2) receptor in the regulation of volume reabsor ption. Systemically administered (intravenous) AT(1) and AT(2) receptor ant agonists, acting through basolateral angiotensin II receptors, have previou sly been shown to inhibit proximal tubule transport. Luminal perfusion of 1 0(-6) mol/L Dup 753 (AT(1) antagonist) and 10(-6) mol/L PD 123319 (AT(2) an tagonist) decreased proximal tubule volume reabsorption from 2.94 +/- 0.18 to 1.65 0.18 and 1.64 +/- 0.19 nL/mm . min, respectively, P < .01. Luminal perfusion of 10(-4) mol/L CGP 42112A, another AT(2) antagonist, similarly d ecreased volume reabsorption to 1.32 +/- 0.36 nL/nm . min, P < .01. The inh ibition of transport with AT(1) and AT(2) antagonist was additive, as lumin al perfusion of 10(-6) mol/L Dup 753 plus 10(-6) mol/L 123319 resulted in a decrease in volume reabsorption to 0.41+/- 0.31nL/ mm . min, P < .001 v co ntrol, P < .05 v Dup 753, and P < .01 v PD 123319. These results show that endogenously produced angiotensin II regulates proximal tubule volume trans port via both luminal AT(1) and AT(2) receptors. (C) 1999 American Journal of Hypertension, Ltd.