title: Mechanism of the cardiovascular responses caused by L-proline microinjected into the supraoptic nucleus of the hypothalamus in unanesthetized rats.
abstract: In the present study, we report on the cardiovascular effects caused by the microinjection of L-proline (L-Pro) into the supraoptic nucleus (SON) in unanesthetized rats: the possible involvement of ionotropic glutamate receptors in the SON, as well as the peripheral mechanisms involved in the mediation of its cardiovascular effects. We compared the L-Pro effects with those caused by the injection of L-glutamate (L-Glu) into the SON. Microinjection of increasing doses of L-Pro into the SON caused dose-related cardiovascular responses in unanesthetized rats that were similar to those observed after the injection of L-Glu. Pretreatment of the SON with either a selective non-NMDA (NBQX) or a selective NMDA (LY235959) glutamate receptor antagonist blocked the cardiovascular response to L-Pro. The dose-effect curve for the pretreatment with increasing doses of LY235959 was shifted to the left in relation to the curve for NBQX, showing that LY235959 is more potent than NBQX in inhibiting the cardiovascular response to L-Pro. On the other hand, the cardiovascular response to L-Glu was only significantly reduced by pretreatment with NBQX (2 nmol/100 nL), but not affected by LY235959 (2 nmol/100 nL). The pressor response to L-Pro was not affected by intravenous pretreatment with the ganglion blocker pentolinium, but it was blocked by intravenous pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP. In conclusion, these results suggest that L-Pro has a selective receptor that is sensitive to ionotropic glutamate receptor antagonists. Its activation in the SON results in vasopressin release into the systemic circulation, causing pressor and bradycardiac responses.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, SP, 14049-900, Brazil, starlopes19@hotmail.com.
authors.forename: Silvana
authors.initials: S
authors.lastname: Lopes-Azevedo
authors.forename: Cristiane
authors.initials: C
authors.lastname: Busnardo
authors.forename: Fernando Morgan Aguiar
authors.initials: FM
authors.lastname: Corrêa
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections; D011392:Proline / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000187:drug effects*
chemical_list: D011392:Proline