AJP - Regulatory, Integrative and Comparative Physiology, Vol 261, Issue 3 665-R669, Copyright © 1991 by American Physiological Society
Effect of V2 antagonist on clearance of arginine vasopressin by isolated perfused rat kidneys
R. Keeler, A. K. Sato, J. R. Claybaugh and N. Wilson
Department of Physiology, University of British Columbia, Vancouver, Canada.
Isolated rat kidneys were perfused with Krebs-Henseleit-bovine serum
albumin solution at a mean pressure of 99 +/- 2.6 mmHg. After control
periods, arginine vasopressin (AVP) was added to the perfusate at a final
calculated concentration of 25 pg/ml (2.5 x 10(-11) M). Urine and perfusate
samples were collected at 15-min intervals for the following 60 min to
measure kidney function and the renal clearance of immunoreactive AVP
(irAVP). At 15-30 min after the addition of AVP, total renal clearance of
irAVP was 1,623 +/- 190 microliters.min-1.g kidney wt-1. Glomerular
filtration accounted for 35 +/- 3.0% of the total clearance, and 65 +/-
10.3% was cleared by peritubular pathways. Of the filtered irAVP, 48 +/-
4.8% was recovered in the urine. To investigate the importance of V2
receptors in the metabolism of AVP, clearance measurements were made in the
presence of the V2 antagonist [d(CH2)5,D-Ile2,Ile4,Arg8]AVP (5 x 10(-9) M).
Total renal clearance of irAVP was reduced by 48% to 848 +/- 79
microliters.min-1.g-1. This reduction was entirely accounted for by the
complete inhibition of peritubular clearance of irAVP. In the presence of
the V2 antagonist, irAVP was cleared only by filtration. The proportion of
filtered AVP recovered in the urine (53 +/- 8.7%) was not significantly
altered by the presence of the V2 antagonist. We conclude that a major
component of the renal clearance of AVP depends on receptor-mediated uptake
of AVP in the kidney cells.
