EFFECTS OF CENTRAL INJECTION OF KYOTORPHIN AND L-ARGININE ON OXYTOCINAND VASOPRESSIN RELEASE AND BLOOD-PRESSURE IN CONSCIOUS RATS

Intracerebroventricular (ICV) administration of an inhibitor of nitric oxide synthase (NOS) increases oxytocin but not vasopressin secretion , in dehydrated rats [38], Surprisingly, central injection of L-argini ne, the substrate for NOS, caused a similar effect, Kyotorphin (L-tyro syl-L-arginine), a dipeptide formed from L-arginine by kyotorphin synt hetase in the brain may mediate this magnocellular response, Therefore , the dose and time responses of hormone release were compared followi ng ICV injection of kyotorphin and L-arginine to conscious rats that w ere normally hydrated or deprived of water for 24 h, In water-sated ra ts, both L-arginine and kyotorphin increased blood pressure and plasma glucose levels coincident with elevating circulating levels of oxytoc in, but not vasopressin, In dehydrated animals, both L-arginine and ky otorphin increased plasma oxytocin levels with a similar time course b ut only kyotorphin decreased vasopressin release, D-arginine, like L-a rginine, stimulated secretion of oxytocin, indicating a nonstereospeci fic effect, A kyotorphin receptor antagonist (L-leucyl-L-arginine) giv en ICV to dehydrated animals elevated plasma oxytocin and prevented th e decrease in vasopressin levels after kyotorphin, Thus, kyotorphin, b ut not L-arginine, appears to attenuate release of vasopressin either directly from magnocellular neurons or indirectly via modulating compe nsatory reflexes activated by the presser response. On the other hand, an excess of L-arginine and kyotorphin within the CNS may mimic the s tress response by augmenting release of oxytocin and activating the sy mpathetic nervous system to increase blood pressure and plasma glucose levels. (C) 1998 Elsevier Science Inc.