Excitatory amino acids in rostral ventrolateral medulla support blood pressure during water deprivation in rats

Abstract

Excitatory amino acids in rostral ventrolateral medulla support blood pressure during water deprivation in rats. Am J Physiol Heart Circ Physiol 286: H1642-H1648, 2004. First published January 8, 2004 10.1152/ajpheart.01004.2003.-Water deprivation is associated with regional increases in sympathetic tone, but whether this is mediated by changes in brain stem regulation of sympathetic activity is unknown. Therefore, this study tested the hypothesis that water deprivation increases excitatory amino acid (EAA) drive of the rostral ventrolateral medulla (RVLM), by determining whether bilateral microinjection of kynurenate (Kyn; 2.7 nmol) into the RVLM decreases arterial pressure more in water-deprived than water-replete rats. Plasma osmolality was increased in 48-h water-deprived rats (313 Ϯ 1 mosmol/ kgH2O; P Ͻ 0.05) compared with 24-h water-deprived rats (306 Ϯ 2 mosmol/kgH2O) and water-replete animals (300 Ϯ 2 mosmol/ kgH2O). Kyn decreased arterial pressure by 28.1 Ϯ 5.2 mmHg (P Ͻ 0.01) in 48-h water-deprived rats but had no effect in water-replete rats (Ϫ5.9 Ϯ 1.3 mmHg). Variable depressor effects were observed in 24-h water-deprived animals (Ϫ12.5 Ϯ 2.4 mmHg, not significant); however, in all rats the Kyn depressor response was strongly correlated to the osmolality level (P Ͻ 0.01; r 2 ϭ 0.47). The pressor responses to unilateral microinjection of increasing doses (0.1, 0.5, 1.0, and 5.0 nmol) of glutamate were enhanced (P Ͻ 0.05) during water deprivation, but the pressor responses to intravenous phenylephrine injection were smaller (P Ͻ 0.05). These data suggest that water deprivation increases EAA drive to the RVLM, in part by increasing responsiveness of the RVLM to EAA such as glutamate. kynurenic acid; glutamate; brain; arterial blood pressure; osmolality THE ROSTRAL VENTROLATERAL medulla (RVLM) plays a crucial role in the maintenance of basal sympathetic activity (for reviews, see Refs. 6,12,29). Indeed, acute bilateral blockade of the RVLM causes marked decreases in arterial pressure and causes the recorded activity of many sympathetic nerves to cease. Moreover, there is evidence that excitatory amino acid (EAA) input into the RVLM underlies at least part of this tonic activity (6, 29). For example, in the cat and rabbit, bilateral blockade of EAA receptors in the RVLM by microinjection of the EAA antagonist kynurenic acid (Kyn) produces a significant decrease in arterial pressure (5). In rats, bilateral Kyn injections into the RVLM generally do not decrease arterial pressure unless inhibitory input from the caudal ventrolateral medulla (CVLM) or nucleus tractus solitarii (NTS) is first eliminated (6,18,27). It has been proposed that in normal rats the tonic excitatory EAA input into the RVLM is balanced by EAA drive of inhibitory interneurons (21, 29). Thus Kyn blocks both the excitatory and inhibitory actions of EAA, and blood pressure does not change significantly.Sympathetic tone does not remain constant but changes in a number of physiological and pathophysiological states. For example, in multiple...

AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation

“…We also show that RVLM AT1Rs are required for BP maintenance in this hypovolemic state, as in sodium deprivation (16), in parallel with tonic excitation of RVLM glutamate receptors (6,7).…”

“…RVLM injection sites were verified against those previously published, within an area ϳ500 m caudal to the caudal end of the facial nucleus and ventral to nucleus ambiguus (see Fig. 5) (6).…”

“…As described above, PVN neurons that project to the RVLM are activated during water deprivation (41,42), and the vast majority of these neurons are glutamatergic (44). Moreover, previous work indicates that the RVLM is tonically excited by glutamatergic inputs during water deprivation (6,7). However, the role of other neurotransmitters has not been previously investigated.…”

Water deprivation activates a glutamatergic projection from the hypothalamic paraventricular nucleus to the rostral ventrolateral medulla

“…In support of the glutamate hypothesis, iontophoretic application of the excitatory amino acid receptor antagonist kynurenic acid attenuates the increase in RVLM unit discharge to chemical and electrical stimulation of the PVH (Yang et al, 2001). In addition, bilateral microinjection of kynurenic acid into the RVLM of water-deprived rats significantly decreased arterial blood pressure (Brooks et al, 2004a). Altogether, these observations suggest that water deprivation may increase sympathetic outflow by recruiting a glutamatergic pathway from the PVH to the sympathoexcitatory neurons of the RVLM.…”

“…The neural pathway from PVH to spinal sympathetic vasomotor efferents is likely to relay in the RVLM (Allen, 2002;Brooks et al, 2004a), a region of dense projection from the PVH which contains the bulk of the bulbospinal sympathoexcitatory blood-pressure regulating neurons (Schreihofer and Guyenet, 1997;Guyenet et al, 1998;Schreihofer and Guyenet, 2000;Stornetta et al, 2002b). However, little is known of the neurotransmitter(s) utilized by RVLM-projecting PVH neurons.…”