Central arginine vasopressin and endogenous antipyresis

Arginine vasopressin (AVP) is a centrally synthesized nonapeptide that exerts classical endocrine effects as well as a host of centrally mediated actions. A strong case can be argued in support of a neurotransmitter–neuromodulator role for AVP. Acting within the central nervous system (CNS), AVP has been demonstrated to be involved in the modulation of febrile body temperature. Because AVP acts to reduce pyrogen-induced fevers, but not normal body temperature, its actions are deemed to be antipyretic. However, to demonstrate an endogenous antipyretic function, AVP must be shown to be active during conditions where fever is naturally suppressed. This review will focus on five such conditions where the absence of pyrogen-induced fever can be linked to the endogenous activity of AVP within the brain. In the neonatal rat pup, the use of specific antagonists to the AVP receptor has revealed a role for CNS AVP in the absence of fever following peripheral injections of bacterial endotoxin. These results may help to explain a similar lack of fever in other newborn species. In parturient animals a reduced or absent febrile response has been linked to the increased presence of AVP within the septal area of the brain. The combined use of AVP receptor antagonism as well as immunohistochemistry has shown enhanced AVP activity within the ventral septal area of the rat and guinea pig brain during tolerance to intravenous pyrogens. These results suggest that the mechanism of fever suppression following repeated systemic injections of bacterial pyrogen includes centrally acting AVP. Recent observations from our laboratory have revealed a suppression of fever during the rising phase of arterial blood pressure in the one-kidney, one-clip model of hypertension. The normal febrile response to prostaglandin E1 can be restored in this instance by blockade of ventral septal AVP receptors. A similar situation of lack of response to pyrogens occurs in hypotensive animals in which pressor mechanisms are activated to restore blood pressure to normal. In this, and the previous four examples, centrally acting AVP has been linked to the natural suppression of pyrogen-induced fevers. Using these models of endogenous antipyresis we will continue to investigate this phenomenon to assess the benefits to the organism as well as to examine other nonthermal host defence responses.