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

When GABA (4-amino-n-butyric acid, 50-200 micrograms) was injected into the lateral ventricle of urethane-anaesthetized Wistar rats, sympathetic nerve activity, arterial pressure and heart rate were decreased dose-dependently. Graded electrical stimulation of the ventromedial hypothalamus (50, 100 and 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 and 200 micrograms, i.c.v.). In spontaneously hypertensive rats (SHR), i.c.v.-injected GABA also reduced sympatho-cardiovascular activity, but the magnitude of the depressor responses was significantly larger in SHR than in normotensive Wistar-Kyoto (WKY) control rats. Pressor and sympathetic nerve responses elicited by hypothalamic stimulation were initially larger in SHR than in WKY rats. However, upon subsequent i.c.v. injection of GABA, hypothalamic responsiveness in SHR was inhibited more prominently and became almost the same as that in WKY rats. These results suggest that, by depressing hypothalamic function, central GABA-ergic stimulation decreases sympathetic nerve activity thereby lowering blood pressure and heart rate. Because of the increased central sensitivity in SHR, GABA-ergic stimulation reversed hypothalamo-sympathetic hyperactivity and attenuated hypertension.
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PMID:Central GABA-ergic stimulation attenuates hypertension and hypothalamic hyperactivity in spontaneously hypertensive rats. 346 96

The activity of glutamate decarboxylase (GAD) in the whole brain, hypothalamus, cerebellum, as well as in the brain after excision of the hypothalamus and cerebellum, is significantly lower in hypertensive rats (SHR) than in normotensive ones (NR). Moreover, the gamma-aminobutyric acid (GABA) turnover rate is lower in the whole brain in SHR. The obtained results indicate that in the arterial hypertension the activity of GABA-ergic system is impaired.
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PMID:The activity of glutamate decarboxylase and the turnover of gamma-aminobutyric acid in spontaneously hypertensive rats. 374 85

To elucidate the role of the central gamma-aminobutyric acid (GABA) system in the maintenance of deoxycorticosterone (DOCA)NaCl hypertension, the responses of mean arterial pressure (MAP), plasma norepinephrine (NE), and epinephrine (EP) to intracerebroventricular (ICV) administration of muscimol, a GABA agonist, and the responses of MAP to bicuculline, a GABA antagonist, and to clonidine, an alpha 2-adrenoceptor agonist known to lower blood pressure by inhibiting sympathetic tone, were examined in conscious, unrestrained 4 week DOCA/NaCl hypertensive rats and age-matched uninephrectomized control rats. Muscimol (50-1000 ng/300 g, ICV) caused dose-dependent decreases in MAP which were greater in DOCA/NaCl rats than in controls. Basal plasma NE and EP were significantly higher in DOCA/NaCl rats than in controls. Muscimol (1000 ng/300 g, ICV) induced decreases in plasma EP which were greater in DOCA/NaCl rats than in controls without changing NE levels in either group. Bicuculline (3 micrograms/300 g, ICV) caused increases in MAP which were the same in both groups. The depressor response to clonidine (5 micrograms/300 g) was greater in DOCA/NaCl rats than in controls. These results suggest that the activity of the central GABAergic system is altered in the rat with established DOCA/NaCl hypertension and that the alteration in central GABAergic function may be related to the increased sympathoadrenal activity and the maintenance of hypertension in this model.
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PMID:Enhanced depressor effect of muscimol in the DOCA/NaCl hypertensive rat: evidence for altered GABAergic activity in brain. 404 65

Neurons of the lower brain stem maintain resting levels of arterial pressure (AP), mediate reflex responses from cardiopulmonary receptors, and are an important site of the hypotensive actions of alpha 2-adrenergic agonists. Details of the pathways and transmitters that mediate tonic and reflex control of AP are emerging. Afferent fibers of cardiopulmonary receptors in the ninth and tenth nerves terminate bilaterally in the nucleus of the tractus solitarius (NTS). Although some neurons contain substance P, the primary neurotransmitter appears to be the excitatory amino acid L-glutamate (L-glu). Neurons in rostral ventrolateral medulla, which most probably comprise the C1 group of epinephrine neurons, are also critical in AP control. C1 neurons project to innervate cholinergic preganglionic sympathetic neurons in the spinal cord. Stimulation of the C1 area electrically or with L-glu increases AP, while lesions or local injection of the inhibitory amino acid gamma-aminobutyric acid (GABA) lowers AP to levels comparable to spinal cord transection. Lesions of C1 neurons or their pathways abolish vasodepressor reflexes from baroreceptors and vagal afferents. In contrast, noradrenergic neurons of the caudal ventrolateral medulla, the A1 group, project rostrally to innervate, in part, vasopressin neurons of the hypothalamus. Stimulation of A1 neurons lowers AP, while lesions or GABA elevates it. We propose that C1 neurons comprise the so-called tonic vasomotor center of the brain stem and also mediate, via a projection from the NTS, the vasodepressor limb of baroreflexes. The NTS-C1 projection may be GABAergic.
Hypertension
PMID:Brain stem catecholamine mechanisms in tonic and reflex control of blood pressure. 615 1

This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central alpha-adrenergic blood pressure regulating mechanisms. Fundamental principles Arterial baro- and chemoreceptor signals reach the nucleus of the tractus solitarius (NTS) via vagal and glossopharyngeal afferents. The NTS communicates with sympathetic preganglionic neurons in the spinal cord via centers and tracts in the medulla, pons, and hypothalamus that include an alpha-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-1 epinephrine cells of the medulla, B-1 and B-3 serotonin cells of the medulla, and A-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded by linked or single genes. New methods of purifying and locating alpha- and beta-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic alpha 2-receptors in a brain stem inhibitory network, which down-regulates these receptors. Alpha 1-receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. Alpha 2-receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although alpha-methylnorepinephrine is probably the principal metabolite of methyldopa, alpha-methylepinephrine and alpha-methyldopamine may also contribute. The site of action usually is identified as the NTS. Possible roles for the descending tracts were suggested. Clinical pharmacology Methyldopa, clonidine, guanfacine, and related drugs lower blood pressure principally by CNS mechanisms but peripheral actions may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:In summary: satellite symposium on central alpha-adrenergic blood pressure regulating mechanisms. 615 4

1. The cardiovascular effects after intracerebroventricular injections of substance P were investigated in normotensive Wistar-Kyoto and in spontaneously hypertensive rats. 2. Substance P increased blood pressor in both rat strains. Wistar-Kyoto rats responded with moderate, dose-dependent blood pressure increases, and heart rate decreased; spontaneously hypertensive rats showed two- to three-fold increased pressor effects and, concomitantly, marked heart rate increases to intracerebroventricular injections of substance P. 3. Sino-aortic baroreceptor denervation rendered Wistar-Kyoto rats supersensitive to intracerebroventricular substance P to a similar degree as unoperated spontaneously hypertensive rats. Sino-aortic denervation had no effect on the blood pressure responses to the peptide in spontaneously hypertensive rats. 4. The central pressure actions of substance P could be markedly attenuated by intracerebroventricular pretreatment with the derivative of gamma-aminobutyric acid, baclofen. 5. We conclude that the baroreceptor reflex is disturbed in spontaneously hypertensive rats. Substance P may contribute to the pathogenesis of hypertension. The effector pathways appear to be different from angiotensin.
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PMID:Blood pressure and heart rate responses to centrally administered substance P are increased in spontaneously hypertensive rats. 616 Sep 41

Despite the availability and application of more effective antihypertensive drugs over the past 3 decades, hypertension continues to be a major risk factor for the development of premature cardiovascular disease. Moreover, failure to elucidate the pathogenesis of essential hypertension, noncompliance, and difficulties in defining the appropriate level of blood pressure elevation requiring therapy, continue to mitigate against the adequate control of hypertension. Some of these problems may be overcome by the availability of depot forms of antihypertensive medication or implantable drug delivery systems, or by the use of several recently developed antihypertensive drugs. These include dopaminergic agonists, selective alpha-adrenergic agents, calcium antagonists, medullary neutral lipids, gamma-aminobutyric acid agonists, and inhibitors of renin or phenethylamine N-methyl-transferase. In addition, the potential involvement of morphinomimetic peptides, prostaglandins, tonin, and bradykinin in blood pressure control or certain hypertensive states suggests that drugs developed to block or potentiate the actions of these substances may have important therapeutic applications.
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PMID:Speculative approaches in hypertension: concepts and drugs of the future. 626 17

3-Mercaptopropionic acid (3-MP), an inhibitor of the synthesis of gamma-aminobutyric acid (GABA), was administered to anesthetized rats and guinea-pigs in order to examine the relationship between the effect of this agent on regional levels of GABA in the brain and cardiovascular function. After a latent period, 3-mercaptopropionic acid (0.16 ml/kg, i.p.) produced initial increases in blood pressure and heart rate in rats followed by vagal bradycardia and hypotension. Guinea-pigs treated with 3-mercaptopropionic acid developed one of three patterns of cardiovascular changes. The type I response consisted of a period of sympathetically-mediated hypertension and tachycardia followed by vagal bradycardia. Type II animals exhibited increased arterial pressure and heart rate, but no vagal activation. Type III and control animals exhibited no significant cardiovascular changes following administration of 3-mercaptopropionic acid or appropriate vehicle. Regional levels of GABA in brain, measured at 90 min after treatment were significantly lower than control in type I and II animals in 3 of 4 areas of the brain measured, but not in type III guinea-pigs. When decreases in levels of GABA were compared to the changes in cardiovascular parameters for individual animals, the decrease in heart rate at the time of sacrifice was directly correlated with the decrease in medullary levels of GABA in type I animals. Conversely, in type II guinea-pigs, decreases in hypothalamic levels of GABA correlated inversely with heart rate at sacrifice. These results suggest that activation of cardiac sympathetic and parasympathetic nervous pathways following the administration of 3-mercaptopropionic acid may result from decreased levels of GABA in different regions of the brain.
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PMID:Cardiovascular effects of 3-mercaptopropionic acid and levels of GABA in regions of the brain of guinea-pigs. 672 26

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

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


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