AJP - Regulatory, Integrative and Comparative Physiology, Vol 245, Issue 5 713-R719, Copyright © 1983 by American Physiological Society
Further in vivo evidence for antagonist-to-antidiuretic action of arginine vasopressin
S. Ishikawa, J. K. Kim and R. W. Schrier
The effect of a new arginine vasopressin (AVP) analogue,
[1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),
2-O-ethyltyrosine, 4-valine]AVP or d(CH2)5Tyr(Et)VAVP, was examined on
exogenous and endogenous AVP in the conscious rat. An intravenous injection
of 8 micrograms/kg body wt of the AVP analogue completely blocked the
antidiuretic effect of exogenous AVP (4 ng/kg body wt iv). Similarly, 8
micrograms/kg of the AVP analogue totally abolished the antidiuretic effect
of infused AVP (0.1 mU X kg-1 X min-1) in the homozygous Brattleboro rats
with central diabetes insipidus. The antagonism of this antidiuretic effect
of exogenous AVP occurred in the absence of changes in urinary solute
excretion, glomerular filtration rate (GFR), and mean arterial pressure.
Intraperitoneal administration of the AVP analogue (30 micrograms/kg body
wt) decreased the mean urinary osmolality in rats after 24 h of fluid
deprivation from 3,098 +/- 140 to 797 +/- 155 mosmol/kg H2O (P less than
0.001). The duration of the antagonism of endogenous AVP was approximately
4.5 h. The antagonism of AVP was not dependent on the vascular properties
of AVP, since the AVP analogue also blocked the antidiuretic effect of
exogenous 1-deamino-8-D-AVP (DDAVP), an AVP analogue with negligible
vascular properties. These in vivo results therefore indicate that
d(CH2)5Tyr(Et)VAVP is a specific antagonist of the hydrosmotic effect of
exogenous and endogenous AVP. In contrast to some previous analogues, this
effect of the AVP analogue occurred in the absence of any known diuretic
factors including an increase in GFR, solute excretion, and blood
pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
