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

Systemic administration of the GABA antagonist picrotoxin 6.0 mg/kg i.v. elicited hypertension and a fall in sinus rate with a return to baseline levels in intact rats. Antagonists of GABA act in the supraspinal CNS to augment sympathetic outflow to the heart and vasculature. Therefore, in this study the spinal cord was transected prior to drug administration in order to eliminate sympathetically mediated effects. In spinal rats, picrotoxin 6.0 mg/kg evoked a biphasic sinus rate response characterized by an initial decrease followed by an increase above baseline sinus rate. Bilateral vagotomy or atropine pretreatment blocked sinus rate changes elicited by picrotoxin, demonstrating that these effects were vagally mediated. Midcollicular decerebration altered the biphasic sinus rate response by preventing the late rise but not the initial decrease in sinus rate. Infusion of another GABA antagonist, bicuculline, elicited a similar biphasic sinus rate response, although the time-course was shorter. Unexpectedly, picrotoxin or bicuculline administration in spinal rats caused an increase in mean blood pressure which was prevented by decerebration and different from that observed in intact rats with respect to time course. In spinal rats pretreatment with a vasopressin antagonist, D(CH2)5Tyr(Me)AVP, blocked the pressor response induced by picrotoxin infusion without altering the biphasic changes in sinus rate. These results suggest that, in the rat: (1) two GABAergic inhibitory mechanisms at different levels of the neuraxis exert opposite effects on cardiac vagal activity; and (2) GABA antagonists may elevate arterial pressure by a mechanism distinct from their previously described sympathoexcitatory effects.
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PMID:Biphasic effects of systemically administered GABA antagonists on cardiac vagal activity. 394 99

In connection with the elucidation of the mechanisms of the acute and chronic haemodynamic stress during cardiac overloading, as well as in investigations on the role of neurotransmitter systems in the genesis of myocardial hypertrophy (MH), we carried out a complex of studies involving modelling of MH induced by treatment of rats with isoprenaline (ISO.) and of rabbits with thyreotom (Tri-iodothyronin +L-Thyroxin). With a view to studying some pathogenetic factors participating in the characteristics of the reproduced pathological states, combinations with oxprenolol, atropine, phentolamine (Phent.) and amino-oxyacetic acid (AOAA), which is a GABA-inhibitor, were also applied. The results of the ECG studies performed are the main object of the present article. Marked MH was found in rats injected for 12 days with Iso. in doses of 2 mg/kg, as well as in rabbits which received thyreotom (accompanied with development of arterial hypertension). Considerable functional and morphological damage (with subendocardial fibrous proliferations) were discovered in rats treated with Iso. +Phent. The combinations of oxprenolol and AOAA manifested a protective effect to rabbits with thyrotoxic disturbances. Evident is also the essential role played by the adrenergic mechanisms in MH pathogenesis.
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PMID:Some functional changes in experimentally induced cardiac overload. 623 Aug 80

Microinjections of GABA and of the specific agonist of GABA receptors, muscimol, in the intermediate nucleus tractus solitarii (NTS) of pentobarbitone anaesthetized cats produced hypertension and tachycardia. The GABA receptor antagonist, bicuculline, had opposite effects and prevented those of muscimol. Therefore, a GABAergic system appears to modulate the cardiovascular regulation within the NTS. d,l-Baclofen also increased blood pressure and heart rate when injected into the same region, but this effect was not antagonized by bicuculline. The mechanism of this action of baclofen is discussed.
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PMID:Evidence for a neuromodulatory role of GABA at the first synapse of the baroreceptor reflex pathway. Effects of GABA derivatives injected into the NTS. 628 6

Evidence supporting the hypothesis that GABA-ergic mechanisms are involved in controlling mammalian cardiovascular function has been reviewed and analyzed. In vivo and in vitro studies with GABA-agonists and GABA-antagonists have revealed that activation of GABA-receptors is involved in the control of blood pressure and heart rate. Further studies conducted with agents that modify central and/or peripheral GABA-ergic systems could lead to the discovery of drugs that might be useful for treating certain cardiovascular disorders in man, such as hypertension and stroke, and should increase our understanding of the pathophysiological bases of such disorders.
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PMID:gamma-Aminobutyric acid and cardiovascular function. 630 35

Earlier behavioral results led to the suggestion that GABA exerts a tonic inhibitory influence in the dorsal periaqueductal gray (DPAG) matter of the rat integrating defensive behavior. In the present experiments, the role of GABAergic mechanisms in the modulation of the autonomic component of the defense reaction was studied. Thus, the effects of intravenous (IV) injections of chlordiazepoxide as well as of intracerebral (IC) injections of midazolam in the dorsal midbrain, on the blood pressure (BP), heart rate (HR) and respiratory increases induced by electrical stimulation of the DPAG were measured in rats anesthetized with urethane. Chlordiazepoxide (10 mg/kg, IV) as well as midazolam (40 and 160 nmol, IC) attenuated the centrally-induced hypertension, without affecting basal BP. The tachycardia induced by aversive brain stimulation was similarly decreased by the benzodiazepines. In addition, the HR baseline was significantly raised by chlordiazepoxide and by the highest dose of midazolam. The tachypnea induced by brain electrical stimulation was also reduced by both benzodiazepines. Basal respiratory rate was slightly, but significantly decreased by chlordiazepoxide as well as by the two doses of midazolam used and to a lesser extent by the vehicle alone. Chlordiazepoxide attenuated the increase in respiratory depth caused by brain stimulation, while basal respiratory amplitude was not affected. The effects of midazolam on this parameter were unclear. Microinjection of bicuculline (5 and 10 nmol) or picrotoxin (0.3 and 1 nmol) into the DPAG increased the BP, HR and respiration, like the electrical stimulation. The latency and duration of bucuculline effects were shorter than those of picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABA modulation of the defense reaction induced by brain electrical stimulation. 631 41

Cerebral glutamate decarboxylase (GAD) activity in DOCA-salt hypertensive rats showed a significant increase in the mesencephalon and a significant decrease in the cerebral cortex and in the cerebellum, compared to that observed in mononephrectomized normotensive animals. Intracerebroventricular (icv) injection of muscimol (0.5, 1 and 2 micrograms), a GABA receptor agonist, produced a dose-dependent decrease in heart rate (HR), significantly greater in freely moving hypertensive animals than in normotensive controls. Muscimol also reduced mean arterial pressure (MAP). The hypotensive effect induced by muscimol (2 micrograms) was significantly higher in hypertensive animals. Ethanolamine-O-sulphate (5, 10, 20 and 40 microM), an inhibitor of GABA breakdown, determined a decrease in MAP and in HR greater in hypertensive than in normotensive rats. Intraperitoneal injection of valproic acid (50-100 mg/Kg/die) for 6 weeks significantly reduced the development of DOCA-salt hypertension in rats. The anti-hypertensive effect became significant during the 4th week and was dose-dependent. DOCA-salt animals, daily treated with 50 mg/Kg of valproic acid, showed an increased pressor response to intravenous injection of phenylephrine (0.1, 0.5 and 1 microgram/Kg). Data strongly support an impairment of cerebral GABA control of blood pressure and heart rate in DOCA-salt hypertensive rats.
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PMID:Increased cardiovascular responsiveness to GABAergic stimulation in DOCA-salt hypertensive rats. 643 10

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

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


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