LACK OF FEVER SUPPRESSION OR CENTRAL AVP RELEASE IN 1K1C HYPERTENSIVERATS

Previous studies from our laboratory showed a transient suppression of the febrile response to intracerebroventricular (i.c.v.) PGE(1) in th e one-kidney, one-clip (1K1C) model of hypertension. This may have bee n due to an enhanced vasopressinergic transmission since arginine vaso pressin (AVP), acting within the central nervous system (CNS), is thou ght to mediate endogenous antipyresis. These initial experiments utili zed a protocol for the induction of 1K1C hypertension which produced a n initial rapid rise in blood pressure, evident by day 4 following sur gery, with a corresponding inhibition of the febrile response. The pre sent experiments utilized a more slowly developing 1K1C hypertension ( evident by day 12 following surgery) to firstly attempt to determine i f inhibition of the febrile response is due to the actual change in bl ood pressure or to neural signals arising from the clipped kidney, and secondly to determine if the concentration of AVP in push-pull perfus ates of the ventral septal area (VSA) of pyrogen-treated sham-operated and 1K1C rats were altered. In urethane-anaesthetized rats, i.c.v. PG E(2) evoked brisk monophasic fevers in both 1K1C and sham-operated ani mals, 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 inhib ition of the febrile response to PGE(2) when a slower developing hyper tension is induced, nor is there an elevated release of AVP into the V SA under our conditions. We conclude that a rapid increase in blood pr essure, and not high blood pressure per se, is required to produce an inhibition of the febrile response.