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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have suggested that the excitatory amino acid L-glutamate is a neurotransmitter released by baroreceptor afferent nerves at their termination in the nucleus tractus solitarii (NTS). In this study we have examined the effect on arterial pressure, heart rate and baroreflex activity of the glutamate antagonist glutamate diethyl ester (GDEE) microinjected into the NTS of 50 rats anesthetized with Chloralose. Bilateral injections of GDEE produced dose dependent transient hypertension. The threshold dose was 2.5 micrograms/NTS and at a dose of 15 micrograms/NTS a maximal rise in arterial pressure and heart rate (from 95 +/- 8.7 mm Hg to 153 +/- 6.4 mm Hg and from 322 +/- 14.7 beats/min to 364 +/- 16.2 beats/min respectively, P less than 0.001, n = 6) occurred. A dose of 15 micrograms/NTS also completely blocked the baroreflex when injections were made bilaterally and it totally antagonized the cardiovascular effects of L-glutamate when injected immediately prior to L-glutamate. The hypertension, the antagonism of L-glutamate, and the blockade of the baroreflex persisted for 20-30 min. In that L-glutamate mediates a baroreflex-like response upon injection into NTS and in that GDEE blocks that response while at the same time blocking the naturally occurring baroreflex, the data are consistent with L-glutamate being a neurotransmitter of baroreflex afferents.
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PMID:Antagonism of the baroreceptor reflex by glutamate diethyl ester, an antagonist to L-glutamate. 626 90

Kainic acid (KA), an analogue of L-glutamate, was microinjected in 0.1 microliter of saline into the nucleus tractus solitarii (NTS) of adult rats. In rats anesthetized with halothane or alpha-chloralose, KA injected unilaterally elicited hypotension, bradycardia, and apnea. The threshold dose was 0.1-0.2 ng (10(-13) mol). Doses greater than 0.2 ng blocked responses to subsequent injections for at least 30 minutes. Doses of KA greater than 15 ng reduced the reflex bradycardia elicited by raising the arterial pressure with phenylephrine and produced arterial hypertension in rats anesthetized with alpha-chloralose or in other rats within 15 minutes of terminating halothane anesthesia. Bilateral injection of KA in doses greater than 15 ng completely blocked baroreflexes and resulted in a dose-dependent elevation of arterial pressure (167 +/- 9.4; P less than 0.001) both in alpha-chloralose-anesthetized rats and in awake rats after the termination of halothane anesthesia. The hypertension rapidly led to pulmonary edema and death. Procaine microinjected also elicited fulminating hypertension; vehicle did not. Doses of KA producing hypertension caused no histological or biochemical evidence of neuronal death. The cardiovascular responses to KA were restricted to sites in the intermediate one-third of NTS and could not be elicited by injection into adjacent sites in brainstem. The results indicate that, in low doses, KA injected into NTS stimulates neurons which mediate the baroreflex, whereas, in higher doses, it produces baroreflex blockade and neurogenic hypertension. The results suggest that fulminating hypertension can be produced by nondestructive perturbations of neurochemical transmission in brain. Since the cardiovascular responses of KA are similar to those produced by microinjection into NTS of the amino acid neurotransmitter glutamic acid, the study adds further support to the hypothesis that L-glutamate is the neurotransmitter released by baroreceptor afferent nerves.
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PMID:Acute hypertension after the local injection of kainic acid into the nucleus tractus solitarii of rats. 746 Feb 3

The aim of the present study was to examine the participation of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats submitted to the renovascular Goldblatt (two-kidney, one clip) procedure. We inhibited or stimulated this area with the use of drugs such as glycine, L-glutamate, or kynurenic acid. (1) Bilateral microinjection of glycine (100 nmol, 200 nL, n = 13) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 177.2 +/- 29.3 to 102.3 +/- 20.9 mm Hg (P < .05), which was similar to the decrease produced by intravenous administration of hexamethonium. The inhibition of RVLM with glycine in normotensive rats produced a decrease in MAP from 106 +/- 17.1 to 59.7 +/- 7.3 mm Hg (P < .05, n = 9). (2) An impressive increase in MAP from 153.3 +/- 16.3 to 228 +/- 34.9 mm Hg (P < .05) occurred in hypertensive rats after microinjection of L-glutamate (50 nmol, 200 nL, n = 6) into the RVLM. The same procedure caused a significant but less intense increase in MAP from 105 +/- 13.8 to 148.3 +/- 24.9 mm Hg in normotensive rats (P < .05, n = 6). (3) A decrease in MAP from 151.6 +/- 25.3 to 96.8 +/- 22.5 mm Hg occurred in hypertensive rats after microinjection of the broad-spectrum glutamate antagonist kynurenic acid (4 nmol, 200 nL, n = 6) into the RVLM, whereas the same procedure did not change MAP in normotensive animals (n = 6). Heart rate was not significantly affected in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Dec
PMID:Role of the rostral ventrolateral medulla in maintenance of blood pressure in rats with Goldblatt hypertension. 749 79

We aimed at (1) determining the distribution of glutamate (Glu)- and gamma-aminobutyric acid (GABA)-containing neurons in the brainstem with projections to the cardioacceleratory sympathetic preganglionic neurons in the intermediolateral nucleus (IML) of the upper thoracic cord and (2) determining whether such afferent projections in spontaneously hypertensive rats (SHR) differ from those of control Wistar-Kyoto (WKY) rats. We used a combination of electrophysiological methods to determine the site of HRP injection in the spinal cord and double-labeling methods for plotting the distribution of Glu- and GABA-immunoreactive neurons with projections to this site. HRP/Glu-labeled neurons (possibly glutamatergic) and HRP/GABA-labeled neurons (possibly GABAergic) were detected in 27% and 7% of the total HRP-labeled neurons of the central autonomic nuclei of 3 SHR rats and 3 WKY rats. HRP/Glu-labeled neurons were distributed predominantly ipsilaterally in 20 nuclei of the medulla oblongata, pons and hypothalamus, while HRP/GABA-labeled neurons were distributed in 7 nuclei of the medulla oblongata. No significant differences were found between the average percentages of HRP/Glu-labeled and HRP/GABA-labeled neurons in SHR and WKY rats. These findings indicate that: (1) the Glu-containing neurons represent a greater proportion than the GABA-containing neurons, (2) the proportions of these neurons appear to be similar in WKY and SHR rats and (3) generation of inbred tachycardia and hypertension in SHR rats can not be attributed to the topological and quantitative differences in the distribution of the glutamatergic and GABAergic neurons in the central autonomic nuclei.
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PMID:Distribution of glutamate- and GABA-immunoreactive neurons projecting to the cardioacceleratory center of the intermediolateral nucleus of the thoracic cord of SHR and WKY rats: a double-labeling study. 751 18

Evidence is accumulating for the role of metabotropic, as well as ionotropic, glutamate receptors in cardiovascular regulation. We sought to determine whether stimulation of metabotropic glutamate receptors in the rostral ventrolateral medulla would evoke enhanced cardiovascular responses in spontaneously hypertensive rats (SHR). Thus, we microinjected (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic glutamate receptors, into the rostral ventrolateral medulla of urethane-anesthetized adult SHR and age-matched Wistar-Kyoto (WKY) rats. Microinjection of (1S,3R)-ACPD (1 nmol/50 nL) produced increases in mean arterial pressure and splanchnic sympathetic nerve activity in SHR (+41 +/- 6 mm Hg and +34 +/- 4%, respectively) that were significantly greater than those observed in WKY rats (+18 +/- 3 mm Hg and +22 +/- 3%, P < .005 and P < .05, respectively). The pressor responses evoked by microinjection of L-glutamate (2 nmol), N-methyl-D-aspartate (20 pmol), or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol) were also significantly (P < .001) augmented in SHR (+55 +/- 3, +61 +/- 7, and +53 +/- 5 mm Hg, respectively, in SHR versus +31 +/- 1, +30 +/- 3, and +28 +/- 2 mm Hg in WKY rats). Results indicate that stimulation of metabotropic, as well as ionotropic, glutamate receptors in the rostral ventrolateral medulla evokes enhanced cardiovascular responses in SHR, which may contribute to hypertension in this model.
Hypertension 1994 Dec
PMID:Role of metabotropic glutamate receptors in ventrolateral medulla of hypertensive rats. 752 93

MEDULLARY ROSTRAL VENTROLATERAL RETICULAR NUCLEUS (RVL): Reticulospinal neurons are critical to control of the circulation by the brain. Its actions are implemented by a few reticulospinal neurons, 200 in the rat. These directly innervate and excite preganglionic sympathetic neurons of the spinal cord by releasing L-glutamate. The RVL-spinal sympathetic premotor neurons are innervated by neurochemically diverse afferents from local and remote sources. They maintain arterial pressure tonically, mediate vasomotor reflexes elicited by stimulation of baro- or chemoreceptors or in response to pain or muscular exercise, and couple vasomotor responses to defense and conditioned fear behaviors. RVL-spinal neurons are central oxygen sensors, directly excited by hypoxia, and initiate sympathetic responses to cerebral ischemia or distortion (Cushing reflex). Stimulation of the RVL directly elevates cerebral flow independently of metabolism and initiates much of the cerebrovascular vasodilation in response to hypoxemia. RVL-SPINAL NEURONS IN RELATION TO HYPERTENSION AND SHOCK: RVL-spinal neurons are sites of action for many centrally acting antihypertensive drugs and some vasoactive hormones. Their integrity is required for expression of the elevated arterial pressure in neurogenic hypertension and for the compensatory sympathetic responses to hemorrhage. We propose that RVL-spinal neurons (1) maintain the activity of sympathetic neurons in mid-range amplifying, thereby, their signaling capacities; (2) initiate and integrate circulatory responses to a lack of oxygen so as to protect the brain from real or threatened hypoxia; (3) maintain, by tonic activity, normal expression of genes and gene products of central and peripheral sympathetic neurons and their peripheral targets that relate to their structure and neurotransmission-associated functions.
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PMID:Sympatho-excitatory neurons of the rostral ventrolateral medulla are oxygen sensors and essential elements in the tonic and reflex control of the systemic and cerebral circulations. 776 86

1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar-Kyoto rats: WKY). 2. Of the brain regions examined the highest kynurenine aminotransferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activity. 3. All samples from SHR showed greatly reduced kynurenine aminotransferase activity compared to WKY. These reductions were most pronounced in the medulla and spinal cord, approximately 45-55%, and lowest in the cerebellum and olfactory bulbs, approximately 25-30%. 4. The kynurenic acid content of the rostral and caudal medulla as well as the spinal cord was also significantly lower in SHR. 5. These results suggest that there may be a deficiency in the kynurenic acid content and kynurenine aminotransferase activity in the SHR. 6. Given the accumulating evidence of the importance of medullary glutamatergic pathways in the control of blood pressure, as well as the higher sensitivity of cardiovascular neurons of SHR to applied glutamate, it seems possible that endogenous kynurenic acid in the brain may play a role in the control of blood pressure and the pathogenesis of experimental hypertension in the SHR.
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PMID:Kynurenic acid, an endogenous glutamate antagonist, in SHR and WKY rats: possible role in central blood pressure regulation. 788 80

Excess dietary sodium is a major contributing factor to the incidence and severity of hypertension. However, the precise mechanism or mechanisms by which salt contributes to the severity of hypertension are unknown. The region of the rostral ventrolateral medulla (RVLM) is a principal brain stem locus critical for the regulation of arterial blood pressure by the sympathetic nervous system. The purpose of this study was to determine if excess dietary sodium chloride might alter the function or responsiveness of neurons in the RVLM. Male Sprague-Dawley rats were given either tap water or 0.9% sodium chloride solution to drink for 10 to 14 days. Excess sodium chloride did not affect baseline blood pressure. However, when neurons of the RVLM were stimulated by microinjections of L-glutamate, evoked increases in arterial pressure were potentiated in rats given sodium chloride. Augmented pressor responses could not be accounted for by increased vascular reactivity because both groups responded similarly to intravenously administered phenylephrine and norepinephrine. Additionally, electrical stimulation of descending spinal sympathoexcitatory axons produced identical pressor responses in both groups, indicating that altered synaptic transmission at central or peripheral neuroeffector junctions distal to the RVLM could not explain enhanced pressor responses produced by direct stimulation of RVLM cell somata. Finally, impaired arterial baroreceptor reflexes could not account for augmented RVLM pressor responses, as depressor and bradycardic responses produced by electrical stimulation of aortic baroreceptor afferents were not reduced in rats given excess dietary sodium chloride.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Dec
PMID:Increased dietary salt sensitizes vasomotor neurons of the rostral ventrolateral medulla. 790 36

Microinjection of the excitatory amino acid L-glutamate into the nucleus tractus solitarii (NTS) elicits decreases in arterial pressure and heart rate. In the present study, we sought to determine the regional hemodynamic effects that were correlated with changes in arterial pressure and heart rate produced by stimulation of the NTS. In anesthetized rats, blood flow in the renal (RBF), superior mesenteric (MBF), and hindquarter (HBF) vascular beds was measured by pulsed Doppler flowmeters. Relative vascular resistances (RVR, MVR, and HVR) were calculated by dividing mean arterial pressure (mm Hg) by the Doppler shift (kHz). Microinjection of L-glutamate into the NTS caused rapid, transient, dose-related decreases in mean arterial pressure and heart rate. MVR and RVR were minimally changed immediately after injections, but both demonstrated delayed dilatation. In contrast, HVR fell immediately but demonstrated delayed constriction. Identical changes occurred in intact rats and in those with interruption of the baroreflex by sinoaortic denervation. Ganglionic blockade with hexamethonium abolished virtually all L-glutamate-induced responses. This study suggests that NTS neurons exert differential effects on renal, mesenteric, and hindquarter vascular beds and that glutamate-induced regional hemodynamic changes are mediated predominantly through autonomic pathways.
Hypertension 1994 Jan
PMID:Hemodynamic effects elicited by stimulation of the nucleus tractus solitarii. 790 59

To examine whether serotonergic mechanisms in the nucleus tractus solitarius (NTS) become altered by hypertension, responses to serotonin (5-HT) or L-glutamate injected into the NTS were compared in anesthetized rats. Because isotonic saline had appreciable effects whereas artificial cerebrospinal fluid did not, artificial cerebrospinal fluid was routinely used as the vehicle. Microinjections of 5-HT or L-glutamate always reduced mean pressure, heart rate, and renal nerve activity. Depressor and bradycardic responses to 5-HT were consistently more pronounced in spontaneously hypertensive rats than in either regular Wistar or Wistar-Kyoto rats, but similar responses elicited with L-glutamate did not differ between rat groups. By contrast, attendant inhibition of renal nerve activity was the same in all rats, thereby suggesting that it either is not a good indicator of sympathetic activity or does not contribute to the hypotensive effects of 5-HT. Our results are compatible with the interpretation that hypotensive responses to 5-HT were enhanced because serotonergic mechanisms for cardiovascular regulation in the NTS were sensitized in spontaneously hypertensive rats.
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PMID:Selective enhancement in SHR of hypotension and bradycardia caused by NTS-injected serotonin. 790 75


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