Does endogenous peripheral arginine vasopressin have a role in the febrile responses of conscious rabbits?
1. The actions of peripheral arginine vasopressin (AVP) on the febrile responses of conscious rabbits induced by peripherally administered polyinosinic:polycytidylic acid (poly(I).poly(C)) have been studied using an AVP V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin). 2. Temperature responses were monitored continuously using rectal thermistor probes. Test substances were administered intravenously (i.v.). Blood samples were taken at timed intervals from a marginal ear vein and plasma PGE2 and PGF2 alpha levels determined by radioimmunoassay. 3. Poly(I).poly(C) (2.5 micrograms/kg) stimulated a reproducible biphasic rise in body temperature with a lag phase of 45-60 min and peaks at 90 and 225 min. The febrile response was accompanied by a 5-fold rise in circulating immunoreactive (ir) PGE2, which peaked after 90 min and remained elevated up to 300 min. Poly(I).poly(C) also stimulated a 2.5-fold rise in circulating irPGF2 alpha, which peaked after 150 min and was followed by a return to basal levels after 300 min. 4. The overall magnitude of the febrile response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. 5. The irPGE2 response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. The irPGF2 alpha response was only reduced at the peak 150 min time point measurement. 6. In conclusion, these results show a modulatory role for a peripherally administered AVP V1 antagonist in the febrile responses to poly(I).poly(C), suggesting a possible propyretic role for endogenous peripheral AVP. This modulatory role appears to be mediated via actions on prostaglandin E2.
Milton
N G
NG
Department of Clinical Biochemistry, University of Newcastle upon Tyne.
Hillhouse
E W
EW
Milton
A S
AS
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D015237:Dinoprost / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D005334:Fever / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007369:Interferon Inducers / Q000494:pharmacology; D008297:Male; D011070:Poly I-C / Q000494:pharmacology; D011817:Rabbits; D014667:Vasopressins / Q000037:antagonists & inhibitors
D065092:Antidiuretic Hormone Receptor Antagonists; D007369:Interferon Inducers; D014667:Vasopressins; D001127:Arginine Vasopressin; C028888:argipressin, deaminopenicillamine(1)-O-methyl-Tyr(2)-; D015237:Dinoprost; D015232:Dinoprostone; D011070:Poly I-C