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

Synaptogenesis of catecholamine (CA) boutons in the nucleus tractus solitarius (NTS) was compared between spontaneously hypertensive (SHR) rats and Wistar-Kyoto (WKY) rats at different ages. On the average, there were about 32 CA varicosities per 2200 microns2 area of the NTS in both SHR and WKY rats as revealed by glyoxylic acid fluorescence microscopic (FM) morphometric study. The FM analysis indicated that there were no significant changes in the CA varicosity density between SHR and WKY rats. The CA boutons were labeled with 5-hydroxydopamine and appeared to contain small granular vesicles at the electron microscopic (EM) level. A total of 1402 CA boutons were studied in a 540,000 micron2 area of the NTS. The number of CA boutons involved in synaptic contacts vs the number of total CA boutons was used to obtain synaptic frequency which was taken as an index for synaptogenesis. A reduction of approximately 18% and 14% of synaptogenesis of CA boutons was observed in the NTS of SHR rats at 4 weeks (prehypertensive stage) and 12 weeks (early hypertensive stage) of age respectively, as compared to age-matched WKY rats. No significant difference of synaptogenesis of CA neurons was found between SHR and WKY rats at 16 weeks of age, a stage in which hypertension is well established and maintained in SHR rats. These results suggest that CA neurons with fewer synaptic contacts in the NTS may play a more important role in the initiation than in the maintenance of hypertension in the SHR rats. In addition to CA terminals, there were numerous GABAergic cell bodies in the NTS which were identified by immunocytochemistry using antibodies to the GABA synthesizing enzyme, L-glutamate decarboxylase (GAD). GABAergic dendrites with GAD-positive reaction were often seen to receive several GAD-negative synapses at EM random profiles. In the text, a viewpoint is thus discussed that emphasizes that a synaptic abnormality of CA terminals with fewer synaptic contacts affecting GABAergic neurons may participate in the pathogenesis of hypertension. However, it remains to be determined as to whether or not there is a direct contact between CA boutons and GABAergic dendrites.
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PMID:Ultrastructural studies on catecholaminergic terminals and GABAergic neurons in nucleus tractus solitarius of the rat medulla oblongata. 673 6

One may postulate a genetic defect in membrane permeability, in the transport of sodium, or in the sodium pump in vascular muscle which could account for increased intracellular sodium and enhanced vascular contractility. If the electrogenic sodium pump is overactive, as in SHR, its inhibition may lead to significant depolarization and greater contraction. Sympathetic innervation may be essential for the development of membrane abnormality as well as for the development of hypertrophic vascular changes, both of which augment contraction and vascular tone. A similar membrane defect at the sensory endings of arterial stretch receptors may account for impaired arterial baroreceptor reflexes seen in very early phases of hypertension or, in some genetic models, before hypertension develops. This defect may be related to the sodium pump or sodium transport in the receptor region and cause a decrease in baroreceptor discharge and in the strain-sensitivity of the baroreceptors, resulting in exaggerated sympathetic drive. Further information is needed on the baroreflex control of various efferents in hypertension. Another membrane defect at the adrenergic nerve terminals may facilitate release of endogenous NE. Excessive salt intake may unmask or exaggerate the membrane defects. In the central nervous system a defect in glutamine, NE, or GABA receptors may contribute to a high central sympathetic drive. Greater receptor affinity to various pressor neuropeptides such as angiotensin and leucine enkephalin or greater release of these peptides may also account for the excessive CNS sympathetic activation or impairment of baroreflexes at a central level. Cardiac receptors may have a variable influence on sympathetic drive in the various stages of hypertension, depending on the degree of cardiac hypertrophy or cardiac size. Finally, increased renal afferent nerve activity may provoke an increase in sympathetic activity and provide a link between natriuretic factors and the sympathetic nervous system in hypertension.
Hypertension
PMID:The sympathetic system in hypertension. State-of-the-art review. 704 Feb 39

Gamma aminobutyric acid (GABA) and different GABA analogues were examined for their cardiovascular actions and their influence on striatal dopamine (DA) levels and GABA accumulation after aminooxyacetic acid (AOAA). Gamma hydroxybutyric acid (GHBA) and baclofen caused hypertension and tachycardia after systemic as well as intracerebroventricular administration, while the opposite was true for GABA and muscimol. The hypertension after GHBA and baclofen was not reduced by picrotoxin or bicuculline and was not influenced by varying GABA levels by 3-mercaptopropionic acid (3-MPA) or AOAA. GHBA and muscimol but not baclofen reduced GABA accumulation induced by AOAA. Picrotoxin in a subconvulsive dose increased GABA accumulation and antagonized the inhibition after GHBA or muscimol. Bicuculline and a moderate dose of picrotoxin tended to decrease GABA accumulation by themselves and if anything augmented the effects of GHBA and muscimol. GHBA and baclofen but not muscimol in combination with AOAA increased DA levels, which was not prevented by picrotoxin or bicuculline. We conclude that the cardiovascular actions of GHBA and baclofen are probably not mediated by mechanisms identical to those of muscimol or exogenous GABA. In view of the biochemical results their actions would however be compatible with a concept of different GABA receptors.
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PMID:Effect of GABA analogues on blood pressure and central GABA metabolism in the rat. 743 98

Recent studies from this laboratory have shown that neurons in this hypothalamic region are stimulated by hypoxia in vivo and in vitro. In addition, GABAergic activity is depressed in the posterior hypothalamus of the spontaneously hypertensive rat compared to the normotensive rat. The major purposes of the present study were to: a) evaluate if posterior hypothalamic neurons respond differently to GABA in the hypertensive rat compared to the normotensive rat; and b) examine the possibility that hypothalamic neurons from spontaneously hypertensive rats respond differently to hypoxia than those from normotensive rats. In addition, the effects of GABA on hypoxia-sensitive neurons was recorded. Extracellular single unit recordings of hypothalamic neurons were performed in a rat brain slice preparation. Neuronal responses to hypoxia (10% O2/5% CO2/85% N2) and to GABA were recorded from slices taken from both Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Administration of three different concentrations of GABA evoked a dose-related decrease in discharge rate in similar percentages of neurons from both SHR and WKY rats. The magnitude of the depression elicited by GABA did not differ significantly between the neurons from SHR and WKY rats. Hypoxia increased the firing rate of 75% and 69% of the SHR and WKY neurons, respectively; no differences (p > 0.05) were noted in the magnitude of the response or in the percentage of neurons responding to hypoxia between the two strains of rats. The discharge rate of most of these neurons fell to below control level following removal of the hypoxic stimulus. A significant percentage of SHR (75%) and WKY (75%) neurons that were stimulated by hypoxia were inhibited by exogenously applied GABA. These results indicate that a) an altered sensitivity of hypothalamic neurons to GABA does not contribute to hypertension in the SHR and b) the depressed respiratory response to hypoxia in the SHR is not due to a decreased responsiveness of hypothalamic neurons to hypoxia.
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PMID:In vitro effects of GABA and hypoxia on posterior hypothalamic neurons from spontaneously hypertensive and Wistar-Kyoto rats. 771 8

The central GABAergic system is associated with normal blood pressure regulation, but the role of GABA receptors in genetic hypertension remains unclear. This study was conducted to investigate GABAA receptor binding in several brain regions of spontaneously hypertensive (SHR) rats during development of hypertension. GABAA receptor binding was labeled with [35S]TBPS and was assessed by quantitative autoradiography with the aid of a computer-assisted image analysis system. Densities of GABAA receptor binding sites were significantly lower in all hypothalamic and amygdaloid nuclei evaluated in 4-week-old SHR rats, when compared with their age-matched normotensive Wistar-Kyoto rats. At 12 weeks of age, GABAA receptor binding remained significantly lower in the central amygdaloid nucleus and paraventricular hypothalamic nucleus of SHR rats. Collectively, the results suggest that GABAA receptors in these nuclei are likely to be involved in the initiation and maintenance of hypertension. In conclusion, this study supports a notion that downregulation of GABAA receptor binding occurs in the hypothalamus and amygdala of SHR rats and may play a role in genetic hypertension.
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PMID:Lower GABAA receptor binding in the amygdala and hypothalamus of spontaneously hypertensive rats. 788 50

Morphological and pharmacological evidence suggest that the dense GABAergic innervation of the supraoptic nucleus is important for regulating the electrical activity of vasopressin and oxytocin neurons. We have employed the technique of intracranial microdialysis to examine extracellular GABA concentrations in the supraoptic nucleus of the anaesthetized rat and questioned whether differences exist in the dynamics of GABA release between virgin and lactating rats, and if events during lactation or following blood pressure manipulation alter endogenous GABA levels in this nucleus. No significant differences were detected between virgin and lactating animals in either basal or 100 mM potassium ion-evoked GABA release. The inclusion of the GABA uptake blocker nipecotic acid (0.5 mM) into the dialysate resulted in a six- to eight-fold increase (P < 0.01) in GABA outflow in both groups of animals. In lactating rats, GABA outflow measured at 4 min intervals was not altered during a 60 min period of suckling by a full litter of pups and no significant change in GABA outflow was detected in relation to individual milk ejections. In virgin rats, removal of 1.5-2 ml of blood resulted in a 30-60 mmHg fall in blood pressure and a non-significant decline in GABA outflow. Replacement of blood resulted in an abrupt 50 mmHg increase in blood pressure and a significant 22% increase in GABA outflow (P < 0.01), but no change in aspartate or methionine concentrations. Repeated intravenous injections of the alpha-adrenoceptor agonist, metaraminol, similarly evoked approximately 50 mmHg increments in blood pressure and a 26% increase in GABA outflow (P < 0.05). Electrical stimulation of the diagonal band of Broca for 10 min produced a two-fold increase in GABA outflow from the supraoptic nucleus (P < 0.05). These results show that the overall profile of basal and potassium-stimulated GABA concentrations in the supraoptic nucleus is not substantially different between lactating and virgin rats. In lactating animals we have found that GABA levels are not altered in response to suckling or at the time of high-frequency firing by oxytocin neurons to induce milk ejection. In contrast, our data further support the hypothesis that GABA inputs to supraoptic neurons are part of a baroreceptor reflex, relaying through the diagonal band of Broca, to signal periods of acute hypertension and inhibit the firing of vasopressin neurons. Such observations suggest the physiological importance of GABA inputs to the supraoptic nuclei and indicate that GABA may be used in a stimulus-specific manner to influence the activity of magnocellular neurons.
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PMID:Extracellular GABA concentrations in rat supraoptic nucleus during lactation and following haemodynamic changes: an in vivo microdialysis study. 789 64

Previous studies demonstrated that stimulation of type B gamma-aminobutyric acid (GABAB) receptors but not type A (GABAA) receptors in the nucleus tractus solitarius of spontaneously hypertensive rats elicited a larger increase in arterial pressure compared with control rats of the Wistar-Kyoto strain. The present studies extended that observation by examining the cardiovascular response to injection into the nucleus tractus solitarius of a selective GABAB receptor antagonist, CGP 35348, in these strains as well as examining the cardiovascular responses to stimulation or blockade of GABAB receptors in the nucleus tractus solitarius in another model of hypertension, the rat treated with deoxycorticosterone acetate and salt. In both groups of hypertensive rats the pressor response to injection into the nucleus tractus solitarius of the GABA uptake blocking drug nipecotic acid was significantly greater compared with control rats (P < .01 in each model). Similarly, in both models of hypertension, the depressor response elicited by blockade of GABAB receptors in the nucleus tractus solitarius by injection of CGP 35348 was approximately 75% greater compared with control rats (P < .05 in each model). These results suggest that alterations in GABAB-mediated neural transmission in the nucleus tractus solitarius may contribute to the elevated arterial pressure observed in these models of hypertension.
Hypertension 1993 Dec
PMID:Enhanced gamma-aminobutyric acid-mediated responses in nucleus tractus solitarius of hypertensive rats. 790 34

The intrathecal application of the GABA-B agonist baclofen has become more and more popular for severe spinal spasticity. Since it was first introduced in 1984 more than 1000 patients worldwide have been treated by this method, using an implantable drug administration device. Clinical data from 48 patients are presented, as well as further experience from a multicentre trial conducted in Europe, in conjunction with a literature overview. The method is now generally accepted as a powerful treatment for spasticity due to spinal lesions of whatever aetiology; improvement in mobility and function as well as relief of spastic pain are the most obvious benefits for the patient. Bladder function is improved in terms of increased bladder volume and lowered residual volume. In patients with supraspinal lesions causing muscle hypertension, where several mechanisms usually contribute besides hyper-reflexia (spasticity), the response has been less pronounced, but intrathecal baclofen still seems to have clinical effects that are superior to those of any oral drug treatment. The initial technical and methodical problems have been solved and today the procedure is generally assessed as safe.
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PMID:Intrathecal baclofen. 814 75

The lateral hypothalamus (LH) is involved in the central integration of fluid and electrolyte balance. Several studies have suggested a role for norepinephrine (NE) in these functions. In previous studies we presented evidence in support of a modulatory role for NE within the LH circuitry. Specifically, NE facilitated responses of LH cells to synaptic inputs and putative transmitters. In the present studies, we examined the influence of NE on the response of LH neurons to the inhibitory amino acid transmitter GABA. Neuronal responses were studied in normal, DOCA hypertensive, and 1% NaCl diet (HSD)-treated rats. Male rats were uninephrectomized and received a DOCA implant (200 mg/kg). They were given 1% NaCl and 0.1% KCl in their drinking water (4-6 weeks). HSD rats received the same treatment, except that no DOCA was given. Extracellularly recorded responses from single LH neurons to iontophoretic pulses (5-50 nA; 10 s duration) of GABA were examined before, during and after NE microiontophoresis (5-50 nA) in anesthetized rats. The results indicated a shift of NE modulatory action from potentiating to antagonizing GABA-induced inhibition. In control rats, NE routinely potentiated GABA depressant responses (19 of 26, 73%), whereas in HSD rats the ability of NE to enhance GABA responses was reduced to 33% of the cases tested (10 of 30). Likewise, NE did not augment, but rather antagonized GABA inhibition in the majority of cells recorded (21 of 35, 60%) from DOCA hypertensive rats. The beta agonist isoproterenol was still capable of potentiating GABA inhibition of LH cells in HSD and DOCA treated animals, suggesting that the change in the capacity of NE to enhance GABA action is not a result of alterations in beta receptor function, but could arise from a modification of the ratio between alpha- and beta-adrenoceptors. NE modulating capability was also altered-in LH neurons responsive to experimentally induced changes in blood pressure. In summary, these findings suggest that chronic HSD and DOCA treatments can alter the modulatory capacities of NE within the LH. These alterations in noradrenergic action within hypothalamic cardiovascular centers might affect the way neurons respond to afferent baroreceptor information, as well as the way they control sympathetic and parasympathetic effector mechanisms. A decrease in the inhibitory capacities of GABA transmission in these areas, due to alterations of NE, may play a role in the genesis of hypertension.
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PMID:Alterations in noradrenergic physiological characteristics with DOCA-hypertension: interaction between norepinephrine and GABA in rat lateral hypothalamus. 818 73

Previous studies indicate a tonic GABAergic inhibitory mechanism in the posterior hypothalamus (PH) contributes to modulating cardiovascular activity. Blockade of GABA receptors on neurons in this area elicits an increase in sympathetic discharge, arterial pressure, and heart rate. It has been proposed that a deficit in this inhibitory system may be responsible for the elevated pressure in the spontaneously hypertensive rat (SHR). The purpose of this study was to determine if the spontaneous neuronal activity in the posterior hypothalamus of spontaneously hypertensive rats differs from that of age-matched normotensive Wistar-Kyoto rats (WKY). Single unit, extracellular recordings of posterior hypothalamic neurons were performed on both in vivo and in vitro preparations. The spontaneous firing rate of posterior hypothalamic neurons in the anesthetized adult SHR was significantly higher (3.66 +/- 0.55 Hz) compared to that of the anesthetized adult WKY rat (2.11 +/- 0.29 Hz). Moreover, more of the neurons in the anesthetized SHR (38%) had a bursting discharge pattern than in the WKY (16%). In order to exclude inputs from peripheral receptors or other brain areas, an in vitro preparation was used. Neurons from both young and adult SHRs also had an increased spontaneous discharge rate and higher percentage of burster-type cells in the posterior hypothalamus compared to neurons from age-matched WKYs in the brain slice preparation. Both the in vivo and in vitro findings support the possibility that an elevated neuronal activity in the posterior hypothalamus, a known pressor area, of the SHR contributes to the development and/or maintenance of hypertension in this animal model.
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PMID:Augmented neuronal activity in the hypothalamus of spontaneously hypertensive rats. 842 Jun 34


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