Acute and chronic increases in osmolality increase excitatory amino acid drive of the rostral ventrolateral medulla in rats

2004 ◽  
Vol 287 (6) ◽  
pp. R1359-R1368 ◽  
Author(s):  
Virginia L. Brooks ◽  
Korrina L. Freeman ◽  
Theresa L. O’Donaughy
Keyword(s):  
Amino Acid ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Excitatory Amino Acid ◽  
Isotonic Saline ◽  
Plasma Osmolality ◽  
Saline Infusion ◽  
Ventrolateral Medulla ◽  
Depressor Response ◽  
Hypertonic Saline Infusion

Water deprivation is associated with increased excitatory amino acid (EAA) drive of the rostral ventrolateral medulla (RVLM), but the mechanism is unknown. This study tested the hypotheses that the increased EAA activity is mediated by decreased blood volume and/or increased osmolality. This was first tested in urethane-anesthetized rats by determining whether bilateral microinjection of kynurenate (KYN, 2.7 nmol) into the RVLM decreases arterial pressure less in water-deprived rats after normalization of blood volume by intravenous infusion of isotonic saline or after normalization of plasma osmolality by intravenous infusion of 5% dextrose in water (5DW). Water-deprived rats exhibited decreased plasma volume and elevated plasma osmolality, hematocrit, and plasma sodium, chloride, and protein levels (all P < 0.05). KYN microinjection decreased arterial pressure by 24 ± 2 mmHg ( P < 0.05; n = 17). The depressor response was not altered following isotonic saline infusion but, while still present ( P < 0.05), was reduced ( P < 0.05) to −13 ± 2 mmHg soon after 5DW infusion. These data suggest that the high osmolality, but not low blood volume, contributes to the KYN depressor response. To further investigate the action of increased osmolality on EAA input to RVLM, water-replete rats were also studied after hypertonic saline infusion. Whereas KYN microinjection did not decrease pressure immediately following the infusion, a depressor response gradually developed over the next 3 h. Lumbar sympathetic nerve activity also gradually increased to up to 167 ± 19% of control ( P < 0.05) 3 h after hypertonic saline infusion. In conclusion, acute and chronic increases in osmolality appear to increase EAA drive of the RVLM.

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

2004 ◽  
Vol 286 (5) ◽  
pp. H1642-H1648 ◽  
Author(s):  
Virginia L. Brooks ◽  
Korrina L. Freeman ◽  
Kathy A. Clow
Keyword(s):  
Arterial Pressure ◽  
Sympathetic Activity ◽  
Excitatory Amino Acids ◽  
Water Deprivation ◽  
Excitatory Amino Acid ◽  
Plasma Osmolality ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Strongly Correlated ◽  
Pressor Responses

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 ± 1 mosmol/kgH2O; P < 0.05) compared with 24-h water-deprived rats (306 ± 2 mosmol/kgH2O) and water-replete animals (300 ± 2 mosmol/kgH2O). Kyn decreased arterial pressure by 28.1 ± 5.2 mmHg ( P < 0.01) in 48-h water-deprived rats but had no effect in water-replete rats (–5.9 ± 1.3 mmHg). Variable depressor effects were observed in 24-h water-deprived animals (–12.5 ± 2.4 mmHg, not significant); however, in all rats the Kyn depressor response was strongly correlated to the osmolality level ( P < 0.01; r2 = 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 < 0.05) during water deprivation, but the pressor responses to intravenous phenylephrine injection were smaller ( P < 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.

Thirst and fluid regulatory responses to hypertonicity in older adults

1996 ◽  
Vol 271 (3) ◽  
pp. R757-R765 ◽  
Author(s):  
N. S. Stachenfeld ◽  
G. W. Mack ◽  
A. Takamata ◽  
L. DiPietro ◽  
E. R. Nadel
Keyword(s):  
Older Adults ◽  
Hypertonic Saline ◽  
Rating Scale ◽  
Isotonic Saline ◽  
Plasma Osmolality ◽  
Free Water ◽  
Saline Infusion ◽  
Renal Handling ◽  
Aging Adults ◽  
Hypertonic Saline Infusion

To assess the fluid regulatory responses in aging adults, we measured thirst perception and osmoregulation during and after infusion of hypertonic NaCl) saline in older (72 +/- 2 yr, n = 6) and younger (26 +/- n = 6) subjects. Hypertonic saline was infused at 0.1 min-1.kg-1 for 120 min. On a separate day, the same subjects were infused identically with isotonic saline as a control. After infusion and a 30-min equilibration period, the drank water ad libitum for 180 min. Hypertonic infusion led to graded increases in plasma osmolality (Posm; 18 +/- 2 and 20 +/- 2 mosmol/kgH2O) and percent changes plasma volume (16.2 +/- 1.9 and 18.0 +/- 1.2%) that were in older and younger subjects. Osmotically stimulated increases in thirst (94.8 +/- 18.9 and 88.3 +/- 25.6 mm), assessed on a line rating scale, and plasma arginine vasopressin concentration (6.08 +/- 1.50 and 4.51 +/- 1.37 pg/ml, for older younger, respectively) were also unaffected by age. subsequent hypervolemia, both groups of subjects sufficient water to restore preinfusion levels of Posm. Renal handling of free water and sodium was also unaffected by age during recovery from hypertonic saline infusion, but was significantly lower in older subjects during recovery from saline infusion, resulting in net fluid retention and a significant fall in Posm (6 mosmol/kgH2O). In contrast to earlier reports of a blunted thirst response to dehydration hypertonicity, we found that osmotically stimulated thirst and renal osmoregulation were intact in older adults after hypertonic saline infusion.

Aortic baroreceptor reflexes are mediated by NMDA receptors in caudal ventrolateral medulla

1987 ◽  
Vol 252 (3) ◽  
pp. R628-R633 ◽  
Author(s):  
F. J. Gordon
Keyword(s):  
Amino Acid ◽  
Arterial Pressure ◽  
Nmda Receptors ◽  
Excitatory Amino Acid ◽  
Ventrolateral Medulla ◽  
Gamma Aminobutyric Acid ◽  
Baroreflex Control ◽  
Caudal Ventrolateral Medulla ◽  
Aortic Nerve ◽  
Baroreceptor Reflexes

The purpose of this study was to identify central nervous system pathways and synaptic receptors that participate in baroreflex control of arterial pressure. Microinjections of excitatory amino acids into the caudal ventrolateral medulla (CVM) of anesthetized rats evoked depressor responses analogous to baroreceptor reflexes. Functional inactivation of CVM neurons produced by microinjection of the gamma-aminobutyric acid receptor agonist muscimol completely abolished baroreflex-mediated decreases in arterial pressure elicited by electrical stimulation of the aortic nerve and markedly reduced depressor responses produced by the excitatory amino acid L-glutamate. In contrast, selective blockade of N-methyl-D-aspartic acid (NMDA) receptors in the CVM abolished synaptically mediated depressor responses evoked by aortic nerve stimulation but not those elicited by L-glutamate, kainic acid, or quisqualic acid injected at the same site. These results indicate that the CVM contains an obligatory synapse in the central aortic baroreflex pathway; neural transmission of aortic baroreceptor information in the CVM is mediated by activation of NMDA receptors; and the neurotransmitter released at CVM synapses may be an excitatory amino acid.

Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men

1991 ◽  
Vol 260 (3) ◽  
pp. R533-R539 ◽  
Author(s):  
C. J. Thompson ◽  
P. Selby ◽  
P. H. Baylis
Keyword(s):  
Blood Glucose ◽  
Linear Regression ◽  
Hypertonic Saline ◽  
Linear Regression Analysis ◽  
Plasma Osmolality ◽  
Saline Infusion ◽  
Intraindividual Variation ◽  
Insulin Tolerance ◽  
Vasopressin Secretion ◽  
Hypertonic Saline Infusion

We have studied the reproducibility of the thirst and arginine vasopressin (AVP) responses to osmotic and hypoglycemic stimulation in healthy volunteers undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined close relationships between the slopes (r = +0.72, P less than 0.05) and the abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group intraindividual component of the variance for the slopes and intercepts was 7 and 0.6%, respectively. There were close correlations between the slopes (r = +0.79, P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the regression lines relating Posmol and thirst, and group intraindividual component of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was infused on four occasions in four subjects, and the results showed that the linear regression lines relating PAVP and Posmol and thirst and Posmol were reproducible within an individual. There were similar falls in blood glucose and elevations in PAVP in both ITTs. No relationship was defined between the fall in blood glucose and either the rise in PAVP or the area under the AVP curve (AUC). The intraindividual component of the variance for the rise in AVP and the AUC was 77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation are highly reproducible, but there is considerable intraindividual variation in the AVP response to hypoglycemia.

scholarly journals Fos, RVLM-projecting neurons, and spinally projecting neurons in the PVN following hypertonic saline infusion

2003 ◽  
Vol 284 (4) ◽  
pp. R945-R953 ◽  
Author(s):  
A. Kantzides ◽  
E. Badoer
Keyword(s):  
Spinal Cord ◽  
Hypertonic Saline ◽  
Paraventricular Nucleus ◽  
Cell Activation ◽  
Plasma Osmolality ◽  
Ventrolateral Medulla ◽  
Intravenous Cannula ◽  
Conscious Rats ◽  
Anterior Posterior ◽  
Hypertonic Saline Infusion

Hypertonic saline (HTS; 1.7 M) infused intravenously into conscious rats increases the production of Fos, a marker of cell activation, in the hypothalamic paraventricular nucleus (PVN). The parvocellular PVN contains subpopulations of neurons. However, which subpopulations are activated by HTS is unknown. We determined whether PVN neurons that innervate the rostral ventrolateral medulla (RVLM) or the spinal cord (important autonomic sites) expressed Fos following HTS. Experiments were performed 24–96 h after chronic implantation of an intravenous cannula. HTS significantly increased the number of Fos-positive cells. In the parvocellular PVN, the maximum number of Fos-positive cells occurred rostral of the anterior-posterior level at which the number of neurons that projected to the medulla or spinal cord peaked. Compared with controls, HTS did not significantly increase the number of double-labeled neurons. These findings demonstrate that an elevation in plasma osmolality activates PVN neurons but not the subgroups of PVN neurons with projections to the RVLM or to the spinal cord.

Sympathetic neural responses to increased osmolality in humans

2006 ◽  
Vol 291 (5) ◽  
pp. H2181-H2186 ◽  
Author(s):  
William B. Farquhar ◽  
Megan M. Wenner ◽  
Erin P. Delaney ◽  
Allen V. Prettyman ◽  
Michael E. Stillabower
Keyword(s):  
Muscle Sympathetic Nerve Activity ◽  
Isotonic Saline ◽  
Plasma Osmolality ◽  
Plasma Norepinephrine ◽  
Sympathetic Outflow ◽  
Neural Responses ◽  
Burst Frequency ◽  
Norepinephrine Concentration ◽  
The Relationship ◽  
Hypertonic Saline Infusion

The purpose of this study was to examine the relationship between osmolality and efferent sympathetic outflow in humans. We hypothesized that increased plasma osmolality would be associated with increases in directly measured sympathetic outflow. Muscle sympathetic outflow was successfully recorded in eight healthy subjects during a 60-min intravenous hypertonic saline infusion (HSI; 3% NaCl) on one day and during a 60-min intravenous isotonic saline (ISO) infusion (0.9% NaCl) on a different day. The HSI provides an osmotic and volume stimulus, whereas the ISO infusion provides a volume-only stimulus. Muscle sympathetic nerve activity was quantified using the technique of peroneal microneurography. Plasma osmolality increased during the HSI but not during the ISO infusion (ANOVA, P < 0.05). Sympathetic outflow differed between the trials (ANOVA, P < 0.05); during the HSI burst, frequency initially increased from 14.6 ± 2.5 to 18.1 ± 1.9 bursts/min; during the ISO infusion, burst frequency initially declined from 14.7 ± 2.5 to 12.0 ± 2.1 bursts/min. Plasma norepinephrine concentration was greater at the end of the HSI compared with the end of the ISO infusion (HSI: 297 ± 64 vs. ISO: 202 ± 49 pg/ml; ANOVA, P < 0.05). We conclude that HSI-induced increases in plasma osmolality are associated with increases in sympathetic activity in humans.

scholarly journals Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

2013 ◽  
Vol 304 (2) ◽  
pp. H303-H310 ◽  
Author(s):  
Britta Veitenheimer ◽  
John W. Osborn
Keyword(s):  
Spinal Cord ◽  
Arterial Pressure ◽  
Osmotic Stress ◽  
Glutamate Receptors ◽  
Kynurenic Acid ◽  
Plasma Osmolality ◽  
Ventrolateral Medulla ◽  
Neurogenic Hypertension ◽  
Conscious Rats ◽  
Salt Hypertension

Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ∼15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.

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