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

Controversy exists as to the neural network whereby peripheral arterial baroreceptor information is transmitted to vasopressin (VP)-secreting neurons of the hypothalamic supraoptic nucleus (s.o.n.). In vivo electrophysiological studies in the rat were undertaken to characterize the selective depression of VP cell activity consequent to activation of peripheral baroreceptors. Electrical stimulation of the diagonal band of Broca (DB) in the rat evoked a similar selective inhibition of vasopressinergic neurons of the s.o.n. Local application of bicuculline, a GABA antagonist, abolished both the DB-evoked and baroreceptor-induced inhibition of VP-secreting neurons. In addition, recordings from DB neurons antidromically activated from the s.o.n. displayed an increase in firing consequent to baroreceptor activation, coinciding with the suppression of firing in s.o.n. VP neurons. These observations collectively indicate that an intrinsic GABA projection arising in the DB cell group selectively inhibits vasopressinergic neurons of the s.o.n. and that this pathway mediates peripheral arterial baroreceptor activity that influences the release of VP in the neurohypophysis. These data may be of critical importance in our understanding the etiology of those forms of experimental hypertension where abnormalities in central baroreceptor pathways have been implicated but not proven.
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PMID:Neurophysiology of a central baroreceptor pathway projecting to hypothalamic vasopressin neurons. 381 62

To determine the central effects of 4-Amino-n-butyric acid (GABA), pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were recorded following the intracerebroventricular (ICV) injection of GABA. In normotensive Wistar rats, anesthetized with urethane, ICV injections of GABA (50-200 micrograms) reduced sympathetic nerve activity, arterial blood pressure, and heart rate in a dose-dependent manner. Graded electrical stimulation of the ventromedial hypothalamus (50, 100, 150 microA) increased not only mean blood pressure but also the rate of sympathetic nerve firing, and both responses were attenuated by GABA pretreatment (100, 200 micrograms, ICV). In spontaneously hypertensive rats (SHR), ICV-injected GABA also reduced sympathetic and cardiovascular activity, but the magnitude of depressor responses was significantly larger in SHR than in normotensive Wister Kyoto controls (WKY). Pressor and sympathetic nerve responses elicited by ventromedial hypothalamic stimulation were initially larger in SHR than in WKY, but upon subsequent ICV injection of GABA, hypothalamic responsiveness in SHR was inhibited more prominently and became comparable to that in WKY. These results suggest that by depressing hypothalamic function, centrally injected GABA decreases sympathetic nerve activity to thereby lower blood pressure and heart rate, and in SHR, ICV-injected GABA reversed hypothalamo-sympathetic hyperactivity and thus attenuated hypertension.
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PMID:Hypotension and hypothalamic depression produced by intracerebroventricular injections of GABA in spontaneously hypertensive rats. 382 May 27

A symposium of over 125 scientists, held in August 1984 at the campus of Oxford University, considered the latest developments concerning cannabis research. Evidence on the mode of tetrahydrocannabinol action on the central nervous system indicates that acetylcholine turnover in the hippocampus through a GABA-ergic mechanism is of major importance, though the role of the dopaminergic or serotoninergic mechanism and involvement of prostaglandins and c-AMP is not ruled out. The use of cannabis causes prominent and predictable effects on the heart, including increased work-load, increased plasma volume and postural hypotension, which could impose threats to the cannabis users with hypertension, cerebrovascular disease or coronary arteriosclerosis. Cannabis or tetrahydrocannabinol has damaging effects on the endocrine functions in both male and female of all animal species tested. Among possible mechanisms of action, it is suggested that tetrahydrocannabinol disrupts gonadal functions by depriving the testicular cells of their energy reserves by inhibition of cellular energetics, and that it stimulates androgen-binding protein secretion, which may account for oligospermia seen in chronic cannabis smokers. In addition to these direct effects on gonads, tetrahydrocannabinol interferes with hormonal secretions from the pituitary, including luteinizing hormones, follicle-stimulating hormones and prolactin. Research findings indicate that maternal and paternal exposure to cannabinoids can influence developmental and reproductive functions in the offspring, but it is difficult to separate possible teratogenic effects from subsequent gametotoxic and mutagenic potentials of cannabinoids.
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PMID:An update on cannabis research. 391 16

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

gamma-Aminobutyric acid (GABA) has been implicated in the development of hypertension and in the regulation of blood pressure. The spontaneously hypertensive rat (SHR) offers an opportunity to explore the role of central GABA and other neurotransmitters in the genesis of high blood pressure. The receptor binding of [3H]GABA, [3H]flunitrazepam, and [3H]glutamate to synaptic membranes from the cerebral cortex and cerebellum of SHR rats were measured in animals of various ages. No significant differences between the SHR and a normotensive control strain of rats were found for any of the assays. The results indicate that in this model of hypertension, neither GABA nor glutamate function are involved, at least not in the cerebral cortex or cerebellum.
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PMID:The GABA/benzodiazepine receptor complex in the nervous system of a hypertensive strain of rat. 614 79

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


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