Neonatal treatment with vasopressin antagonist dP[Tyr(Me)2]AVP, but not with vasopressin antagonist d(CH2)5[Tyr(Me)2]AVP, inhibits body and brain development and induces polyuria in the rat.
Two vasopressin antagonists, d(CH2)5[Tyr(Me)2]AVP and dP[Tyr(Me)2]AVP, were given to Wistar rats from postnatal day 1 to 21 in order to investigate the influence on development and later diuresis. The latter antagonist significantly reduced body growth from day 3 postnatally onwards. At postnatal day 35 body, total brain, cerebellar and kidney weights were significantly reduced compared with controls. Diuresis, measured at one month of age, was four- to five-fold higher than the control group. Combined treatment with vasopressin failed to abolish the weight disturbances or polyuria. However, animals treated with the vasopressin antagonist d(CH2)5[Tyr(Me)2]AVP did not show developmental or diuretic deficits. Allometric analysis of brain/body relationship of the young animals indicated a disturbance of brain development by dP[Tyr(Me)2]AVP. Although the body and brain growth retardation induced by dP[Tyr(Me)2]AVP supports the hypothesis of a role for vasopressin in brain ontogeny, it can also be the result of a nonAVP-related toxic effect, since it could not be prevented by concomitant treatment with vasopressin.
Snijdewint
F G
FG
Netherlands Institute for Brain Research, Amsterdam.
Boer
G J
GJ
D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D008297:Male; D011141:Polyuria / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D014882:Water-Electrolyte Balance / Q000187:drug effects
D001127:Arginine Vasopressin; C028888:argipressin, deaminopenicillamine(1)-O-methyl-Tyr(2)-; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-