Neuropeptide specificity of prostaglandin E2-induced activation of splenic and renal sympathetic nerves in the rat

Abstract Sympathetic activation occurs rapidly following intracerebroventricular (icv) injection of prostaglandin E 2 ( PGE 2 ) . This study examined whether neuropeptides mediate PGE 2 -induced sympathetic nerve activation in urethane/chloralose-anesthetized Sprague–Dawley rats. Animals were pretreated (20.0 μg, icv) with the following receptor antagonists; CRF ([ d -Phe 12 ,Nle 21,38 ,C α -MeLeu 37 ]CRF 12–41 ), AVP-V 1 (Des-Gly-[Phaa 1 , d -Tyr(Et) 2 ,Lys 6 ,Arg 8 ]-vasopressin), or OT (OT+V 1 , [ d ( CH 2 ) 5 , Tyr ( Me ) 2 , Orn 8 ]-vasotocin) followed 20 min later by PGE 2 (2.0 μg, icv). Pretreatment with the CRF antagonist attenuated the increase in renal nerve activity induced by PGE 2 when measured 10 and 30 min post-injection. PGE 2 -induced renal nerve activity was also inhibited at both time points by the AVP antagonist and, to a similar extent, the OT antagonist. The AVP antagonist did not effect splenic nerve responses to PGE 2 whereas the CRF antagonist produced an incomplete and transient reduction in PGE 2 -induced activation of the splenic nerve. However, the OT antagonist completely blocked the activation of the splenic nerve after central injection of PGE 2 . ICV injections of AVP and OT produced immediate changes in splenic and renal nerve activity whereas CRF failed to alter the activity of either nerve in anesthetized or conscious animals. Thus, PGE 2 acts through neuropeptide-specific pathways to initiate sympathetic outflow and OT is a specific component of the sympathetic pathway innervating the spleen.