We report on the cardiovascular effects of
L-glutamate (L-glu) microinjection into the hypothalamic paraventricular nucleus (PVN) as well as the mechanisms involved in their mediation. L-glu microinjection into the PVN caused dose-related pressor and tachycardiac responses in unanesthetized rats. These responses were blocked by intravenous (i.v.) pretreatment with the
ganglion blocker
pentolinium (PE; 5 mg/kg), suggesting sympathetic mediation. Responses to L-glu were not affected by local microinjection of the selective non-
NMDA receptor antagonist
NBQX (2 nmol) or by local microinjection of the selective
NMDA receptor antagonist
LY235959 (LY; 2 nmol). However, the tachycardiac response was changed to a bradycardiac response
after treatment with
LY235959, suggesting that
NMDA receptors are involved in the L-glu heart rate response. Local pretreatment with
LY235959 associated with systemic PE or dTyr(CH(2))(5)(Me)AVP (50 microg/kg) respectively potentiated or blocked the response to L-glu, suggesting that L-glu responses observed after
LY235959 are
vasopressin mediated. The increased pressor and bradycardiac responses observed after LY + PE was blocked by subsequent i.v. treatment with the V(1)-vasopressin receptor antagonist dTyr(CH(2))(5)(Me)AVP, suggesting
vasopressin mediation. The pressor and bradycardiac response to L-glu microinjection into the PVN observed in animals pretreated with LY + PE was progressively inhibited and even blocked by additional pretreatment with increasing doses of
NBQX (2, 10, and 20 nmol) microinjected into the PVN, suggesting its mediation by local non-
NMDA receptors. In conclusion, results suggest the existence of two glutamatergic pressor pathways in the PVN: one sympathetic pathway that is mediated by
NMDA receptors and a vasopressinergic pathway that is mediated by non-
NMDA receptors.