Lack of fever suppression or central AVP release in 1K1C hypertensive rats.
Previous studies from our laboratory showed a transient suppression of the febrile response to intracerebroventricular (i.c.v.) PGE1 in the one-kidney, one-clip (1K1C) model of hypertension. This may have been due to an enhanced vasopressinergic transmission since arginine vasopressin (AVP), acting within the central nervous system (CNS), is thought to mediate endogenous antipyresis. These initial experiments utilized a protocol for the induction of 1K1C hypertension which produced an initial rapid rise in blood pressure, evident by day 4 following surgery, with a corresponding inhibition of the febrile response. The present experiments utilized a more slowly developing 1K1C hypertension (evident by day 12 following surgery) to firstly attempt to determine if inhibition of the febrile response is due to the actual change in blood pressure or to neural signals arising from the clipped kidney, and secondly to determine if the concentration of AVP in push-pull perfusates of the ventral septal area (VSA) of pyrogen-treated sham-operated and 1K1C rats were altered. In urethane-anaesthetized rats, i.c.v. PGE2 evoked brisk monophasic fevers in both 1K1C and sham-operated animals, with no significant difference between fever heights. Consistent with this, we found no increase in immunoreactive AVP from perfusates of the VSA of 1K1C rats. These results suggest that there is no inhibition of the febrile response to PGE2 when a slower developing hypertension is induced, nor is there an elevated release of AVP into the VSA under our conditions. We conclude that a rapid increase in blood pressure, and not high blood pressure per se, is required to produce an inhibition of the febrile response.
Earle
M L
ML
Department of Neuroscience, Faculty of Medicine, University of Calgary, Alta, Canada.
Horn
T
T
Kasting
N
N
Landgraf
R
R
Pittman
Q J
QJ
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D005334:Fever / Q000188:drug therapy*; D006977:Hypertension, Renal / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D001127:Arginine Vasopressin; D000527:Alprostadil