UMLS:C0020538 - FACTA Search

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

We examined the role of central GABAergic mechanisms in salt-induced hypertension and exaggerated responses to stress in borderline hypertensive rats (BHR), the first offspring of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The studies were done in conscious BHR and WKY on high (H) (8% NaCl) or normal (N) (0.3% NaCl) salt diets for 5 weeks. A high-salt diet elevated arterial pressure (AP) (p < 0.01) and augmented pressor responses to shaker stress (p < 0.05) in BHR but not in WKY. Intravenous hexamethonium caused a greater decrease in AP in BHR-H than in BHR-N at rest. Muscimol (a GABA agonist) injected into the central ventricle (i.c.v.) caused a greater decrease in resting AP (p < 0.01) and heart rate (HR) (p < 0.05) and BHR-H than in BHR-N. Renal sympathetic nerve activity (RSNA) did not change in BHR-H, but increased (p < 0.05) in BHR-N during muscimol-induced hypotension, although the magnitudes of muscimol-induced hypotension were greater in BHR-N than in BHR-N. The increases in RSNA in response to intravenous nitroglycerin were similar in BHR-N and BHR-N. Muscimol attenuated pressor and tachycardic responses to stress more in BHR-N than in BHR-N (p < 0.01). Muscimol did not alter AP and HR at rest or their responses to stress in the two groups of WKY. The magnitudes of pressor response to bicuculline (a GABA antagonist) did not differ between the two groups of BHR. These results suggest that a high salt diet may alter the central GABAergic system in BHR, which contributes to salt-induced hypertension and augmented pressor and tachycardic responses to stress.
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PMID:Central GABAergic mechanisms are defective in salt-induced hypertension in borderline hypertensive rats. 874 6

L-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain L-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The L-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, L-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic beta-adrenoceptors to facilitate dopamine release and postsynaptic D2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy. In lower brainstem, L-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABAA receptors, L-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. L-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic L-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release L-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of "L-DOPAergic receptors" with extremely high affinity and low density.
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PMID:Neurobiology of L-DOPAergic systems. 889 95

To determine whether central GABA (gamma-aminobutyric acid) B receptor stimulation would affect the sympathetic and cardiovascular activities, baclofen (a GABAB receptor agonist) was injected into lateral cerebral ventricles (intracerebroventricularly, ICV) in urethane-anesthetized normotensive rats. Intracerebroventricular injections of GABAA agonist (muscimol, 1 microgram) consistently decreased blood pressure and heart rate. In contrast ICV injections of baclofen (2 micrograms) increased blood pressure (BP) and heart rate with initial transient cardiovascular depression, and these effects of baclofen were abolished by ICV pretreatment with GABAB antagonist (saclofen, 100 micrograms). To determine whether the cardiovascular effects of ICV injections were elicited by activating GABA receptors in the hypothalamus, we injected baclofen or muscimol directly into various hypothalamic areas. Baclofen (100 and 800 ng) injected into the ventromedial hypothalamus (VMH) or posterior hypothalamus (PH) of normotensive rats produced dose-related decreases in sympathetic nerve activity, blood pressure, and heart rate. These effects of baclofen were larger in VMH injections than in PH injections. The depressor responses elicited by VMH injections of baclofen were abolished by intravenous pretreatment with alpha-blocker, but unaffected by parasympathetic blocker, further indicating that the depressor responses of baclofen (VMH) were not due to parasympathetic activation, but due to peripheral sympathetic depression. Muscimol (400 ng) and baclofen (800 ng) injected into VMH produced similar amplitude of sympathetic-depressant, depressor and bradycardic responses. In contrast, BP was increased by the same dose of baclofen injected into the hypothalamic depressor area (anterior hypothalamus, AH), but was unaffected by muscimol. Final experiments were performed to determine whether these sympathetic and cardiovascular effects to hypothalamic GABAB stimulations would be altered in hypertension. In spontaneously hypertensive rats (SHR), basal BP and heart rate were already higher than in normotensive controls (Wistar-Kyoto rat, WKY). Baclofen injected into VMH reduced sympathetic nerve activity, BP, and heart rate in both groups of rats, and these effects were significantly larger in SHR than in WKY. This enhanced depressor response induced by baclofen (VMH) in SHR persisted even after sinoaortic denervation, which indicates that the enhanced depressor response is not due to reduced peripheral baroreflex sensitivity in SHR. On the other hand, baclofen injected into AH increased BP and heart rate in both WKY and SHR, but the magnitude of these responses did not differ between two groups. In summary, GABA reduces sympathetic nerve activity, BP, and heart rate through both GABAA and B receptors in VMH. The GABAB system acts on the depressor area, AH, to further regulate the cardiovascular activities. In SHR, the GABAB-ergic system in VMH but not in AH is altered, and this might contribute to the development of hypertension.
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PMID:GABAB-ergic stimulation in hypothalamic pressor area induces larger sympathetic and cardiovascular depression in spontaneously hypertensive rats. 889 48

1. To determine whether hypothalamic and medullary GABA (gamma-aminobutyric acid)B stimulation would affect the sympathetic and cardiovascular activities, and to determine whether these effects would be altered in hypertension, baclofen (a GABAB agonist) was injected into a hypothalamic pressor area (ventromedial hypothalamus, VMH), a depressor area (anterior hypothalamus, AH), or a nucleus tractus solitarius (NTS) in normotensive and spontaneously hypertensive rats (SHR). 2. Intracerebroventricular (ICV) injections of a GABAA agonist (muscimol, 1 mu g) decreased blood pressure (BP) and heart rate (HR). ICV injections of baclofen (2 mu g) elicited biphasic depressor and pressor effects, and these effects were abolished by a pretreatment with saclofen (GABAB antagonist, 100 mu g, icv). 3. Muscimol (400 ng) and baclofen (800 ng) injected into VMH decreased sympathetic nerve activity (SNA), BP and HR to almost similar levels, while saclofen injected into VMH increased HR without affecting BP levels. 4. The same dose of baclofen injected into AH increased BP, but muscimol (AH) did not alter BP. 5. Both muscimol and baclofen injected into NTS increased BP, but its magnitude was larger in baclofen injections. 6. Depressor and sympatho-inhibitory effects of baclofen (VMH) in SHR were larger than those in normotensive Wistar-Kyoto (WKY) rats, while pressor responses elicited by baclofen (AH) did not differ between SHR and WKY. 7. In summary, GABA reduces SNA, BP and HR through both GABAA and GABAB receptors in VMH. In addition, the GABAB system acts on AH and NTS to further regulate the cardiovascular activities. In SHR, GABAB-ergic dysfunction in VMH but not in AH might contribute to the development of hypertension.
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PMID:Hypothalamic and medullary GABAA and GABAB-ergic systems differently regulate sympathetic and cardiovascular systems. 907 40

Spinal cord injury destroys bulbospinal amino acid-containing pathways to sympathetic preganglionic neurons and severely disrupts blood pressure control, resulting in resting or postural hypotension and episodic hypertension. Almost all immunoreactivity for the excitatory amino acid L-glutamate has been reported to disappear from autonomic areas of the cord caudal to a transection, apparently depriving autonomic neurons of their major excitatory input. However, the magnitude of the neurogenic episodic hypertension after cord injury suggests that excitatory inputs to sympathetic preganglionic neurons must still be present. Moreover, the hypotension associated with high spinal injuries may reflect a enhanced role for inhibitory transmitters, such as GABA. This apparent contradiction regarding the presence of glutamate and lack of information about GABA prompted the present investigation. In rats seven days after spinal cord transection, we examined identified sympathetic preganglionic neurons caudal to the injury for the presence of synapses or direct contacts from varicosities that were immunoreactive for the amino acids, L-glutamate and GABA. Adrenal sympathetic preganglionic neurons were retrogradely labelled with cholera toxin B subunit and amino acid immunoreactivity was revealed with post-embedding immunogold labelling. In single ultrathin sections, 46% (98/212) of the synapses or direct contacts on adrenal sympathetic preganglionic neurons were immunoreactive for glutamate and 39% (83/214) were immunoreactive for GABA. Analysis of inputs with the physical disector yielded similar results for the two amino acids. The proportions of glutamatergic or GABAergic synapses on cell bodies and dendrites were similar. When alternate ultrathin sections were stained to reveal glutamate or GABA immunoreactivity, either one or the other amino acid occurred in 78.4% (116/148) of inputs; 4.1% (6/148) of inputs contained both amino acids and 17.5% (26/148) of inputs contained neither. These results demonstrate that nerve fibres immunoreactive for the neurotransmitter amino acids, glutamate and GABA, provide most of the input to sympathetic preganglionic neurons caudal to a spinal cord transection. Synapses containing glutamate and GABA could provide the anatomical substrate for the exaggerated sympathetic reflexes and the low sympathetic tone that result from spinal cord injury.
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PMID:Glutamate- and GABA-immunoreactive synapses on sympathetic preganglionic neurons caudal to a spinal cord transection in rats. 928 72

We investigated in conscious, freely moving rats whether the release of GABA, taurine and arginine in the hypothalamus is influenced by impulses originating from peripheral baroreceptors. The posterior hypothalamic nucleus was superfused with artificial cerebrospinal fluid through a push-push cannula and the release of amino acids was determined in the hypothalamic superfusate of control rats, as well as of rats after bilateral aortic denervation (AD). AD led to hypertension and increased the lability of arterial pressure. In sham-operated rats, intravenous infusion of phenylephrine increased blood pressure and the hypothalamic release of GABA and taurine. AD almost abolished the phenylephrine-induced release of the inhibitory amino acids. Similarly, the pressor response to hypervolaemia, elicited by blood injection, enhanced the release rates of GABA and taurine only in sham-operated rats. Baroreceptor unloading evoked either by intravenous infusion of nitroprusside, or by haemorrhage, decreased the release rates of GABA and taurine in sham-operated rats but not in AD rats. Electrical stimulation of the afferent aortic depressor nerve enhanced extracellular GABA and taurine in the posterior hypothalamic nucleus. The release rate of arginine was not influenced by alterations in baroreceptor activity either in sham-operated or in AD rats. The findings support the idea that, in the hypothalamus, GABA and taurine are involved in central blood pressure regulation. The release of these two amino acids seems to be driven tonically by baroreceptor impulses. Moreover, the findings indicate that the baroreceptors of the aortic arch play a crucial role in the mediation of changes in hypothalamic GABA and taurine outflow so as to counteract blood pressure fluctuations.
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PMID:The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations. 930 72

Hypertension in the conscious rat, elicited by i.v. infusion of phenylephrine, evoked expression of the immediate early gene c-fos in discrete groups of brain stem neurons. Fos-immunoreactive neurons were located in the caudal ventrolateral medulla (CVLM); others were located in the nucleus of the tractus solitarius (NTS). Because of their sensitivity to alterations in arterial pressure, these neurons are likely to subserve the arterial baroreceptor reflex. The aim of this study was to identify the brain stem projections and the neurotransmitter content of the barosensitive CVLM neurons using neuronal tracing and immunohistochemistry. Some of the barosensitive CVLM neurons projected directly to the rostral ventrolateral medulla (RVLM), and many contained the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD). Other CVLM neurons, containing markers of glutamate or catecholamine synthesis, were insensitive to baroreceptor stimulation. This study delineates neuronal pathways acting in the arterial baroreceptor reflex and identifies precisely GABA-synthesizing CVLM neurons as the source of inhibitory input to the RVLM.
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PMID:c-fos identifies GABA-synthesizing barosensitive neurons in caudal ventrolateral medulla. 933 8

Agonists of the GABA-A receptor are neuroprotective after experimental stroke, but studies of GABA-B agonists have contradicted each other. To further investigate whether GABA-B agonists may be neuroprotective, we devised a quantal bioassay using the intraluminal occlusion method of inducing reversible cerebral ischemia. Subjects underwent middle cerebral artery occlusion for varying amounts of time, ranging from 5 to 90 min. Behavioral outcome was measured 48 h later with a quantal observational scale: score of abnormal given for any one of asymmetric forepaw flexion on tail lift, asymmetric grip, circling, reduced exploration, seizures, or death. To the grouped response data the logistic equation was used to find the ED50, the duration of occlusion that caused one-half of the subjects to be abnormal. To find the potency ratio for each drug, we divided the ED50 for treatment by that for vehicle. We administered baclofen, a GABA-B agonist, intraperitoneally 5 min after the onset ofischemia. Baclofen (20 mg/kg) was neuroprotective (potency ratio of 3.0, P < 0.05), but a lower dose (10 mg/kg) was not. However, both doses of baclofen caused significantly more intracerebral hemorrhages than control. In awake animals, both baclofen doses caused significant increases in mean arterial pressure, but no changes in other cardiorespiratory variables. The glutamate antagonist MK-801, the GABA-A agonist muscimol, and hypothermia were all protective using the bioassay (potency ratios ranging from 1.5 to 3.0). We conclude that although baclofen (20 mg/kg) may be neuroprotective, its utility is complicated by postischemic hypertension and cerebral hemorrhages.
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PMID:High dose baclofen is neuroprotective but also causes intracerebral hemorrhage: a quantal bioassay study using the intraluminal suture occlusion method. 934 59

We studied the developmental alteration of GABA release in spontaneous ly hypertensive(SHR) and normotensive Wistar-Kyoto rat(WKY) brain. The release of [3H]GABA observed under high potassium(30 mM) in eleven-week-old(hypertensive) SHR hippocampus and the spontaneous release of [3H]GABA in the same aged SHR medulla oblongata were lower than those of age-matched WKY. We conclude that the GABAergic mechanisms may be different in SHR and WKY brain and may be associated with the development of hypertension.
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PMID:Age-related decrease of gamma-aminobutyric acid (GABA) release in brain of spontaneously hypertensive rats. 949 61

Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present clinically with an identical neurological syndrome. Symptoms include severe abdominal pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction. These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor weakness and sensory involvement, which correlate with peripheral axonal neuropathy, and mental symptoms occurring without clear morphological findings in the cerebrum. The pathogenetic mechanisms which lead to the neurological dysfunction have remained poorly understood, partly due to the lack of a suitable animal model of these rare disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase deficient mice are presented. The present evidence suggests that multiple mechanisms interact in causing the varied symptoms, including ALA interaction with GABA receptors, altered tryptophan metabolism, and possibly heme depletion in nerve cells.
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PMID:Acute porphyrias: pathogenesis of neurological manifestations. 951 77

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