Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To reveal the functional importance of amino acid neurotransmission in the amygdala (AMY) of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, the in vivo release of glutamate (GLU) and GABA in this brain structure was studied using the push-pull superfusion technique. Basal GLU and GABA release rates in the AMY were comparable in SHR and WKY rats, although arterial blood pressure (BP) in SHR (152+/-6 mmHg) was higher than in WKY rats (102+/-4 mmHg). Neuronal depolarization by superfusion with veratridine enhanced the release of GLU and GABA to a similar extent in both rat strains. On the other hand, exposure to noise stress (95 dB) for 3 min led to a tetrodotoxin-sensitive increase in GLU release in the AMY of SHR, but not WKY rats. The concurrent pressor response to noise was enhanced in SHR as compared to WKY rats. A rise in BP induced by intravenous infusion of phenylephrine for 9 min had no effect on amino acid release in the AMY of both strains. The data suggest an exaggerated stress response of glutamatergic neurons in the AMY of SHR as compared with WKY rats, which might be of significance for the strain differences in the cardiovascular and behavioural responses to stress. The results also show that, in both rat strains, glutamatergic and GABAergic neurons in the AMY are not modulated by baroreceptor activation. Moreover, hypertension in adult SHR does not seem to be linked to a disturbed synaptic regulation of glutamatergic or GABAergic transmission in the AMY.
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PMID:Release of glutamate and GABA in the amygdala of conscious rats by acute stress and baroreceptor activation: differences between SHR and WKY rats. 1079 97

Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.
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PMID:High-dose pyridoxine as an 'anti-stress' strategy. 1085 91

Sympathetic storm phenomena are well known therapeutic problems in patients with severe brain injury. We have treated four patients with intrathecal baclofen (ITB) who suffered from severe hypertension, tachycardia and other sympathetic storm phenomena after different primary events. In all patients conventional therapy with sedatives and antiadrenergic medication had been taken to the upper limits before initiating ITB. Autonomic dysfunction immediately improved in three of four patients. In all patients ITB, via lumbar or ventricular route, proved safe and without complications. The anatomical and pharmacological basis of the GABA-B agonist action on such sympathetic storm phenomena are not yet fully understood. However, the positive results observed in three out of four patients are promising and require further investigation. ITB is a new therapeutic approach to control otherwise unresponsive sympathetic storm phenomena in severe brain injury.
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PMID:Intrathecal baclofen alleviates autonomic dysfunction in severe brain injury. 1093 9

Recent years have seen rapid and significant advances in our understanding of the G-protein-coupled gamma-amino butyric acid, B-type (GABA(B)) receptor, which could be a therapeutic target in conditions as diverse as epilepsy and hypertension. This progress originated with the ground-breaking work of Bernhard Bettler's team at Novartis who cloned the DNA encoding a GABA(B) receptor in 1997. Currently, the receptor is thought to be an unusual, possibly unique, example of a heterodimer composed of homologous, seven-transmembrane-domain (7TMD) subunits (named GABA(B) R1 and GABA(B) R2), neither of which is fully functional when expressed alone. The large N-terminal domain of the GABA(B) R1 subunit projects extracellularly and contains a ligand binding site. The similarity of the amino acid sequence of this region to some bacterial periplasmic amino acid-binding proteins of known structure has enabled structural and functional modelling of the N-terminal domain, and the identification of residues whose substitution modulates agonist/antagonist binding affinities. The intracellular C-terminal domains of the R1 and R2 subunits appear to constitute an important means of contact between the two subunits. Alternative splice variants, a common and functionally important feature of 7TMD proteins, have been demonstrated for the R1 subunit. Notably GABA(B) R1a differs from GABA(B) R1b by the possession of an N-terminal extension containing two complement protein modules (also called SCRs, or sushi domains) of unknown function. The levels at which each of the respective variants is expressed are not equal to one another, with variations occurring over the course of development and throughout the central nervous system. It is not yet clear, however, whether one variant is predominantly presynaptically located and the other postsynaptically located. The existence of as yet unidentified splice variants, additional receptor subtypes and alternative quaternary composition has not been ruled out as a source of receptor heterogeneity.
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PMID:The metabotropic GABA receptor: molecular insights and their functional consequences. 1113 Apr 63

We examined the role of the central nervous system, and particularly the renin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L-arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA(A) agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model.
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PMID:Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats. 1121 29

The interrelationship between the breakdown of the blood-brain barrier according to the Evans-blue passage and an abrupt increase in blood pressure (DeltaP) was studied in rats subjected to adrenaline-induced acute hypertension and also pentylenetetrazol-induced seizures. Arterial blood pressure was increased by adrenaline, then immediately i.v. nifedipine was injected and subsequently decreased to the control value in the acute hypertensive group. Arterial blood pressure was increased by pentylenetetrazol, then immediately GABA (gamma-aminobutiric acid) was injected and the blood pressure was decreased to the control value in the seizure group. The animals were divided into five groups. Group I: control; Group II: acute hypertension; Group III: acute hypertension + nifedipine; Group IV: seizure; Group V: seizure + GABA. The Evans-blue dye content was found to be 0.25 +/- 0.01 mg% in the whole brain in the control animals, and 0.803 +/- 0.1 mg% in the acute hypertensive group. This difference between these groups was found to be significant: P< 0.01. In the nifedipine group (Group III) the Evans-blue content was 0.30 +/- 0.1 mg% in the whole brain; and there was no significant difference between control values and nifedipine-treated animals (P> 0.5). The Evans-blue content was 1.6 +/- 0.2 mg% in the whole brain during seizure, and decreased to 0.36 +/- 0.1 mg% after GABA injection was administered. There was also no significant difference between the control value and the GABA-treated animals (P> 0.5). These results have shown that an abrupt increase in blood pressure (DeltaP) did not change the blood-brain barrier permeability in both acute hypertension and seizures.
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PMID:Influence of an abrupt increase in blood pressure on the blood-brain barrier permeability during acute hypertension and epileptic seizures. 1152 87

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. Alterations in the following substances are discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, and corticotropin-releasing factor. Functional changes in these substances occur throughout the hypothalamus but are particularly prominent rostrally; most lead to an increase in sympathetic nervous activity which is responsible for the rise in arterial pressure. A few appear to be depressor compensatory changes. The majority of the hypothalamic changes begin as the pressure rises and are particularly prominent in the young rat; subsequently they tend to fluctuate and overall to diminish with age. It is proposed that, with the possible exception of the Dahl salt-sensitive rat, the hypothalamic changes associated with hypertension are caused by renal and intrathoracic cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a result of renal ischemia and trauma as in the reduced renal mass rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it is submitted, is due to the associated documented impaired ability to excrete sodium. It is proposed, therefore, that the hypothalamic changes in hypertension are a link in an integrated compensatory natriuretic response to the kidney's impaired ability to excrete sodium.
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PMID:The hypothalamus and hypertension. 1158 98

The effect of blockade of ionotropic GABA and glutamate receptors in the rostral ventrolateral medulla (RVLM) on the relationship between phrenic nerve, splanchnic sympathetic nerve and lumbar sympathetic nerve activities was examined in urethane anesthetized, paralyzed and vagotomized Sprague-Dawley rats. Bilateral microinjection of the GABA-A receptor antagonist, bicuculline (4 mM, 100 nl), into the RVLM dramatically, and almost exclusively, increased the post-inspiratory related discharge in both splanchnic sympathetic nerve and lumbar sympathetic nerve activities and elicited hypertension with fluctuations of arterial pressure phase locked to the discharge of the phrenic nerve. Subsequent bilateral microinjection of kynurenate, a non-selective ionotropic excitatory amino acid receptor antagonist (50 mM, 100 nl), into the RVLM significantly attenuated the sympathoexcitation and hypertension evoked by injection of bicuculline. This was accompanied by an abolition of the post-inspiratory related burst discharge of splanchnic sympathetic nerve and lumbar sympathetic nerve activities. These data suggest that the GABAergic inputs to RVLM tonically inhibit glutamatergic inputs from central respiratory neurons that normally act to increase the firing of presympathetic neurons in the RVLM. Inputs from post-inspiratory neurons appear to be an especially potent excitatory synaptic drive to the presympathetic neurons in the absence of the GABAergic inhibition.
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PMID:Evidence for a tonic GABA-ergic inhibition of excitatory respiratory-related afferents to presympathetic neurons in the rostral ventrolateral medulla. 1174 95

We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in gamma-amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbetagal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.
Hypertension 2002 Feb
PMID:Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats. 1184 95

Experimental evidence indicates that the hypothalamic paraventricular nucleus modulates sympathetic vasomotor tone and blood pressure and that this modulation is altered in some cardiovascular diseases. This study tested the hypothesis that this nucleus exerts a more significant tonic excitatory modulation of basal sympathetic vasomotor activity in spontaneously hypertensive rats. In anesthetized, artificially-ventilated rats, bilateral microinjections of the GABA(A) receptor agonist, muscimol (1 to 1.5 nmoles per side), into the paraventricular nucleus produced a depressor and sympathoinhibitory response that did not recover. When compared with normotensive rats, this response was more marked in spontaneously hypertensive rats, where lumbar sympathetic nerve discharge was reduced by 75 +/- 3% and mean arterial pressure fell from 119 +/- 7 mm Hg to 58 +/- 3 mm Hg. Blockade of excitatory and inhibitory amino acid receptors in the rostral ventrolateral medulla significantly attenuated this response. Microinjections of small volumes (<20 nL) of GABA were used to localize precisely the responsive region of the paraventricular nucleus. Unilateral injections of GABA into the dorsomedial cap of the paraventricular nucleus induced a brisk depressor (decrease of 42 +/- 4 mm Hg), sympathoinhibitory (decrease by 72 +/- 2%), and bradycardic (decrease of 77 +/- 16 bpm) response. The mechanisms underlying the sympathoinhibition after inactivation of the paraventricular nucleus are not elucidated, but evidence discussed suggests the involvement of a supracollicular sympathoinhibitory pathway. The results presented demonstrate that the paraventricular nucleus exerts a powerful, tonic effect on the control of sympathetic vasomotor tone under basal conditions in anesthetized rats and that this is enhanced in spontaneously hypertensive rats.
Hypertension 2002 Feb
PMID:Inhibition of the hypothalamic paraventricular nucleus in spontaneously hypertensive rats dramatically reduces sympathetic vasomotor tone. 1184 97


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