ILOPROST, A STABLE ANALOG OF PGI(2), POTENTIATES THE HYPERTHERMIC EFFECT OF PGE(2) IN RATS

Centrally mediated effects of iloprost, a stable analogue of PGI(2), o n rectal temperature have been investigated in conscious rats. ICV adm inistration of iloprost (100-1,000 ng, ICV) produced a dose-dependent, monophasic hyperthermic response that was not inhibited by indomethac in. When injected into the preoptic anterior hypothalamic (POAH) regio n, iloprost (2-50 ng/POAH) induced a biphasic increase in rectal tempe rature. While the first phase was inhibited by AH 6809, an E(1)-type p rostaglandin (EP(1)) receptor antagonist, the second phase was abolish ed by indomethacin pretreatment. Iloprost was found not to alter recta l temperature when injected into the ventromedial hypothalamic area. A dministration of iloprost into the POAH in a dose that had no effect o n rectal temperature significantly potentiated the hyperthermic effect of PGE(2) (50 ng, ICV). These findings suggest that the pyrogenic eff ect of iloprost is partly mediated by EP(1) receptors located on the P OAH. Regarding the similarities of iloprost and PGI(2), it is further proposed that endogenous PGI(2) might act to modulate hyperthermic eff ects of PGE(2) released during arachidonic acid- or endogenous pyrogen -induced fever.