Central mechanism of the cardiovascular responses caused by L-proline microinjected into the paraventricular nucleus of the hypothalamus in unanesthetized rats.
Previously, we reported that microinjection of L-proline (L-Pro) into the paraventricular nucleus of the hypothalamus (PVN) caused vasopressin-mediated pressor responses in unanesthetized rats. In the present study, we report on the central mechanisms involved in the mediation of the cardiovascular effects caused by the microinjection of L-Pro into the PVN. Microinjection of increasing doses of L-Pro (3-100nmol/100nL) into the PVN caused dose-related pressor and bradycardic responses. No cardiovascular responses were observed after the microinjection of equimolar doses (33nmol/100nL) of its isomer D-Proline (D-Pro) or Mannitol. The PVN pretreatment with either a selective non-NMDA (NBQX) or selective NMDA (LY235959 or DL-AP7) glutamate receptor antagonists blocked the cardiovascular response to L-Pro (33nmol/100nL). The dose-effect curve for the pretreatment with increasing doses of LY235959 was located at the left in relation to the curves for NBQX and DL-AP7, showing that LY235959 is more potent than NBQX, which is more potent than DL-AP7 in inhibiting the cardiovascular response to L-Pro. The cardiovascular response to the microinjection of L-Pro into the PVN was not affected by local pretreatment with Nω-Propyl-l-arginine (N-Propyl), a selective inhibitor of the neuronal nitric oxide synthase (nNOS), suggesting that NO does not mediate the responses to L-Pro in the PVN. In conclusion, the results suggest that ionotropic receptors in the PVN, blocked by both NMDA and non-NMDA receptor antagonists, mediate the pressor response to L-Pro that results from activation of PVN vasopressinergic magnocellular neurons and vasopressin release into the systemic circulation.
Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Silvana
S
Lopes-Azevedo
Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Cristiane
C
Busnardo
Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil. Electronic address: fmdacorr@fmrp.usp.br.
Fernando Morgan Aguiar
FMA
Corrêa
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D011392:Proline / Q000008:administration & dosage*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
D002317:Cardiovascular Agents; D002491:Central Nervous System Agents; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D011392:Proline
Cardiovascular response; Ionotropic glutamate receptors; L-Proline; Oxide nitric; Paraventricular nucleus of the hypothalamus (PVN)