Involvement of the glutamatergic system in the paraventricular and supra-optic nucleus on the modulation of the cardiovascular system and the vasopressin and oxytocin release, in rats submitted to osmotic stimuli.

Abstract

ABSTRACTThe supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus contain magnocellular cells that secrete vasopressin (AVP) and oxytocin (OT), which are involved in water balance and cardiovascular function control, as well as in parturition and lactation. Previous studies from our laboratory have shown that a chemical stimulation of the SON or the PVN with L-glutamate (L-glu) caused pressor responses mediated by a systemic release of vasopressin. Glutamate is the major excitatory amino acid in the CNS, being present in glutamatergic synapses in these hypothalamic nuclei. There is evidence of an involvement of glutamate in the release of AVP and OT after an osmotic stimulus in isolated preparations of the hypothalamus. The intravenous (iv) or intraperitoneal (ip) of hypertonic saline is a classic osmotic stimulus for the release of AVP and OT. The present project aims to study the effect of a pharmacological ablation of the NSO or NPV on the plasma concentrations of AVP and OT as well as on cardiovascular effects in response to the intraperitoneal administration of hypertonic saline, in vivo. We will perform bilateral microinjections of 1 mM cobalt chloride (CoCl2, synaptic inhibitor) into the SON of rats with a bilateral lesion of the PVN, or the PVN of rats with bilateral lesion of the SON. Furthermore, we will study the glutamatergic receptor subtype involved in the release of these hormones, and the cardiovascular responses triggered by the osmotic stimulus. To do this, we will apply bilateral microinjections of LY235959 (2 nmol/100nL; a selective antagonist of NMDA subtype of glutamate receptors) or NBQX (2 nmol/100nL; a selective antagonist of glutamate receptors subtype of non-NMDA) into the SON of rats with bilateral lesion of the PVN, or into the PVN of rats with bilateral lesion of the SON.