TY - JOUR
T1 - Effect of luminal angiotensin II receptor antagonists on proximal tubule transport
AU - Quan, Albert
AU - Baum, Michel
PY - 1999/5
Y1 - 1999/5
N2 - The proximal tubule can endogenously synthesize and secrete luminal angiotensin 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 volume reabsorption, which is a reflection of sodium transport within this segment. In this study, we use in vivo microperfusion of angiotensin II receptor antagonists into the lumen of the proximal tubule to examine the role of the luminal AT1 and AT2 receptor in the regulation of volume reabsorption. Systemically administered (intravenous) AT1 and AT2 receptor antagonists, acting through basolateral angiotensin II receptors, have previously been shown to inhibit proximal tubule transport. Luminal perfusion of 10-6 mol/L Dup 753 (AT1 antagonist) and 10-6 mol/L PD 123319 (AT2 antagonist) 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 AT2 antagonist, similarly decreased volume reabsorption to 1.32 ± 0.36 nL/nm min, P < .01. The inhibition of transport with AT1 and AT2 antagonist was additive, as luminal perfusion of 10-6 mol/L Dup 753 plus 10-6 mol/L 123319 resulted in a decrease in volume reabsorption to 0.41 ± 0.31 nL/mm min, P < .001 v control, P < .05 v Dup 753, and P < .01 v PD 123319. These results show that endogenously produced angiotensin II regulates proximal tubule volume transport via both luminal AT1 and AT2 receptors.
AB - The proximal tubule can endogenously synthesize and secrete luminal angiotensin 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 volume reabsorption, which is a reflection of sodium transport within this segment. In this study, we use in vivo microperfusion of angiotensin II receptor antagonists into the lumen of the proximal tubule to examine the role of the luminal AT1 and AT2 receptor in the regulation of volume reabsorption. Systemically administered (intravenous) AT1 and AT2 receptor antagonists, acting through basolateral angiotensin II receptors, have previously been shown to inhibit proximal tubule transport. Luminal perfusion of 10-6 mol/L Dup 753 (AT1 antagonist) and 10-6 mol/L PD 123319 (AT2 antagonist) 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 AT2 antagonist, similarly decreased volume reabsorption to 1.32 ± 0.36 nL/nm min, P < .01. The inhibition of transport with AT1 and AT2 antagonist was additive, as luminal perfusion of 10-6 mol/L Dup 753 plus 10-6 mol/L 123319 resulted in a decrease in volume reabsorption to 0.41 ± 0.31 nL/mm min, P < .001 v control, P < .05 v Dup 753, and P < .01 v PD 123319. These results show that endogenously produced angiotensin II regulates proximal tubule volume transport via both luminal AT1 and AT2 receptors.
KW - CGP 42112A
KW - DUP-753
KW - In vivo microperfusion
KW - PD-123319
KW - Renin-angiotensin system
UR - http://www.scopus.com/inward/record.url?scp=0033041989&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033041989&partnerID=8YFLogxK
U2 - 10.1016/S0895-7061(99)00018-7
DO - 10.1016/S0895-7061(99)00018-7
M3 - Article
C2 - 10342788
AN - SCOPUS:0033041989
SN - 0895-7061
VL - 12
SP - 499
EP - 503
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 5
ER -