Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Adenosine is an inhibitory neuromodulator in several brain regions. In the nucleus tractus solitarius (NTS), however, adenosine exerts excitatory cardiovascular effects. The purpose of the present study was to elucidate the involvement of other endogenous mechanisms that could contribute to the final hemodynamic response to adenosine in this nucleus. In normotensive Sprague-Dawley rats, intra-NTS microinjection of adenosine (2.3 nmol/60 nl) decreased blood pressure and heart rate. These effects were blocked by prior administration of the specific adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol) and by the two glutamate receptor antagonists kynurenic acid and glutamic diethylester. The specificity of the adenosine-glutamate interaction in the NTS was demonstrated with adrenergic and angiotensin receptor antagonists that did not affect the adenosine response and by experiments with glutamate receptor antagonists that did not affect nicotine actions in the NTS. Furthermore, an increase in glutamate levels was demonstrated during perfusion of adenosine through a microdialysis probe in the NTS of anesthetized rabbits. These findings indicate that adenosine increases the release of glutamate in the NTS and, thus, are at variance with the concept of a "universal" inhibitory effect of adenosine in the central nervous system.
Hypertension 1991 Oct
PMID:Cardiovascular excitatory effects of adenosine in the nucleus of the solitary tract. 168 Aug 12

Using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY) and cats, either glutamate or a glutamate receptor subtype agonist was injected into the subretrofacial nucleus (SRF) in the rostral ventrolateral medulla at the site where the pressor response had been evoked by electrical stimulation. The sensitivity of SRF neurons to the electrical stimulation or glutamate receptor agonist was estimated by the threshold current or dose required to evoke the pressor response. The threshold of SRF neurons to electrical stimulation was similar in the three animal groups, while that to the glutamate receptor agonist was different. The significance of the difference in threshold between WKY and SHR was calculated as was that between WKY and cats. The threshold for kainate stimulation was ten times lower for SHR (0.016 pmol, P less than 0.001) and five times higher for cats (0.78 pmol, P less than 0.05); that for quisqualate stimulation was fifty times lower for SHR (0.016 pmol, P less than 0.001) but similar for cats; that for NMDA stimulation was twelve times lower for SHR (0.13 pmol, P less than 0.001) but seven times higher for cats (11 pmol, P less than 0.01); that for glutamate stimulation was ten times lower for SHR (4.2 pmol, P less than 0.001) but similar for cats. The heart rate and respiratory responses associated with the pressor response were tachycardiac and hypopneic in SHR and WKY, but bradycardiac and hyperpneic in cats. These responses were less dominant than the pressor response. We suggest that the pathogenesis of hypertension in SHR may be partly due to abnormal properties of glutamate receptor subtypes acting on vasomotor control neurons in the SRF.
...
PMID:Difference in sensitivity of cardiovascular and respiratory control neurons in the subretrofacial nucleus to glutamate receptor subtype agonists in SHR, WKY and cats. 168 69

Intracisternal (i.c.) administration of the glutamate-receptor antagonist kynurenate to halothane-anesthetized rats (paralyzed, ventilated) produced an initial hypertension associated with an increase in lumbar sympathetic nerve discharge. Kynurenate (i.c.) blocked or greatly reduced all sympathetic reflexes investigated (somatosympathetic 70% reduction; vagal pressor and depressor responses, 100%; hypothalamic mixed responses, 90%; baroreflex, 100%) and increased the firing rate of reticulospinal sympathoexcitatory cells of the rostral ventrolateral medulla (PGCL-SE neurons) by 33%. After i.c. kynurenate, these cells exhibited a rhythmic, non-bursting firing pattern which could be reset by spinal cord stimulation only when antidromic spikes were elicited. Cells with similar characteristics were recorded in the nucleus paragigantocellularis lateralis (PGCL) in an in vitro rat bulb preparation perfused through the basilar artery. Their 'pacemaker-like' discharge pattern was observed even in the absence of kynurenate and was reset by orthodromic activation. Cells with similar characteristics were also recorded within the PGCL in 500-microns coronal slices in vitro. At 37 degrees C their discharge rate was similar to that of PGCL-SE neurons recorded in vivo after i.c. kynurenate; it was also pacemaker-like and was insensitive to glutamate receptor blockade. It is suggested that the tonic discharge of PGCL-SE neurons is normally due to an intrinsic pacemaker activity which is modulated in vivo by a variety of synaptic inputs.
...
PMID:Sympathoexcitatory neurons of rostral ventrolateral medulla exhibit pacemaker properties in the presence of a glutamate-receptor antagonist. 283 Sep 40

Vagal baroreflexes were studied by measuring the atropine-sensitive cardioinhibition produced by raising arterial pressure with phenylephrine in anesthetized rats pretreated with the beta-adrenergic receptor antagonist nadolol. Sympathetic baroreflexes were determined in halothane-anesthetized rats by measuring the inhibition of lumbar sympathetic discharge produced by elevating arterial pressure with gradual aortic constriction. Both reflexes were drastically reduced by bilateral injections of 2.2 nmol of the glutamate receptor antagonist kynurenic acid (KYN) into either the nucleus of the solitary tract (NTS) or the ventrolateral medulla between 0 and 1 mm posterior to the level of the obex. Injections of KYN elsewhere in the medulla were generally ineffective and injections of 8-OH kynurenate (an inactive analog) into the ventrolateral medulla or NTS were also without effect. KYN injections (2.2 nmol) into the intermediate portion of the NTS produced small increases in mean arterial pressure (0-15 mm Hg) and no change in heart rate while injections of similar amounts into the ventrolateral medulla at obex level were followed by large (35-116 mm Hg) increases in pressure and bradycardia. Both types of injections produced a similar degree of blockade of vagal and sympathetic baroreflexes. These results support previous evidence that baroreceptor primary afferents may release a glutamate-like transmitter in the NTS and indicate that a similar type of excitatory transmitter is involved at the level of the ventrolateral medulla in mediating or modulating both vagal and sympathetic baroreflexes. Finally the bradycardia and hypertension produced by blocking amino acid receptors in the ventrolateral medulla appear largely unrelated to the disruption of peripheral baroreceptor inputs.
...
PMID:Role of excitatory amino acids in rat vagal and sympathetic baroreflexes. 356 46

This review concerns the acute phase of stroke. It describes incidence, prevalence, etiology, diagnosis and treatment together with the possibilities for prevention. The incidence of stroke in the Danish population is about 2/1000 person years and has been largely unchanged during the last 20 years. About 85 per cent of strokes are caused by cerebral infarcts, ten percent by intracerebral haemorrhages and about five per cent by subarachnoid bleeding. The incidence increases with age. Up till age 65 years the ratio between men and women is two to one, while the ratio in the oldest age group approaches one to one. The most important risk factors for stroke are smoking, arterial hypertension, previous cerebrovascular disease, heart disease and diabetes mellitus. Till now, no treatment has been documented as effective in reducing the cerebral damage caused by acute stroke. Ongoing controlled clinical trials in the acute state of ischaemic stroke are testing the effect of thrombolytic therapy, treatment with calcium antagonists, glutamate receptor antagonists, aspirin and heparin. The general medical treatment including nursing and physiotherapy in the acute phase is described. Within recent years benefit of various strategies of stroke prevention has been documented.
...
PMID:[Apoplexy--the acute stage]. 841 52

Stroke is an ischemic event in 80% and hemorrhagic in 20%, which can be distinguished by computed tomography of the brain. Unfortunately, no routinely applicable therapy is available for stroke. Several thrombolysis studies are underway and their results will become available in the next few years. Hemodilution has been abandoned except for hematocrits above 50%. Calcium antagonists such as nimodipine reduce vascular spasms after subarachnoidal hemorrhage, but their administration after ischemic stroke is unsuccessful. A new experimental approach is offered by glutamate receptor antagonists, which may prevent cell damage induced by the excitatory amino acid glutamate. In the case of cardio-embolic stroke, heparin should be started after 48 hours. Hypertension should only be treated above values of 200/120 mm Hg, with short-acting intravenous drugs. Because of the limited therapeutic options for completed stroke, primary prevention (treatment of hypertension, anticoagulation for atrial fibrillation) and secondary prevention after transitory ischemic attacks (endarterectomy for carotid stenosis > 70%, aspirin) should be intensified.
...
PMID:[Stroke]. 848 81

A standard electrical stimulus applied to the posterior hypothalamus evoked cardiac arrhythmogenic responses in the spontaneously hypertensive rat. Isolated premature ventricular beats or doublets and nonsustained ventricular tachycardic salvos were observed. This effect was associated with a large rise in blood pressure (79 +/- 3 mm Hg). The same stimulus in normotensive Wistar-Kyoto rats produced no significant cardiac arrhythmias, and the rise in blood pressure was smaller (36 +/- 2 mm Hg). We investigated the influence of baclofen, a GABAB receptor agonist, and two N-methyl-D-aspartate receptor antagonists on the arrhythmogenic response to hypothalamic stimulation. Intravenous baclofen (3 mg/kg) had no effect in the normotensive Wistar-Kyoto rats, but in the spontaneously hypertensive rats it enhanced the adjusted mean value of the number of extrasystoles from 0.5 +/- 0.5 to 18 +/- 1 (P < .001). This value was also increased (from 3 +/- 1 to 17 +/- 1, P < .001) by an intracisternal injection of baclofen (1 micrograms/kg). This facilitatory effect of baclofen was prevented by treatment with atenolol (0.5 mg/kg). Two glutamate receptor antagonists, ketamine (7.5 mg/kg IV) and kynurenic acid (200 micrograms/kg intracerebroventricularly), prevented both the arrhythmogenic response to the hypothalamic stimulation and its facilitation by baclofen. The study confirms that hypothalamic stimulation facilitates the development of arrhythmias through a sympathetic drive and that these arrhythmias are easier to induce in spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. Both the central GABAergic and the glutamatergic systems are implicated in the development of these ventricular arrhythmias, since baclofen could disinhibit the glutamatergic central pathway. These results could account for the ability of the spontaneously hypertensive rats to develop ventricular arrhythmias of central origin.
Hypertension 1996 Jan
PMID:GABAergic and glutaminergic modulation of centrally evoked arrhythmias in rats. 859 79

The microinjection of L-glutamate (1-6 nmol/rat) and N-methyl-D-aspartate (NMDA 1-10 nmol/rat), ionotropic glutamate receptor (iGluR) agonists, into the nucleus raphe obscurus caused a concentration -dependent increase of arterial blood pressure. In contrast, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD, 14-42 nmol/rat), a metabotropic glutamate receptor (mGluRs) agonist, caused a concentration-dependent decrease in blood pressure. Pretreatment with D,L-2-amino-phosphono valeric acid (2-APV, 5 nmol/rat) a selective NMDA iGluR antagonist, and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b] cyclohepten-5,10-imine hydrogen maleate (MK801, 0.9 nmol/rat), a noncompetitive NMDA iGluR antagonist, blocked both the glutamate and NMDA pressor responses, while pretreatment with (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 0.05 nmol/rat), a mGluR1 antagonist, increased the glutamate-induced pressor effects and blocked the fall in blood pressure induced by t-ACPD. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.4 nmol/rat) a non-NMDA iGluR antagonist, did not affected the glutamate-induced hypertension. These observations indicate opposing roles for ionotropic and metabotropic receptors in the glutamate-induced blood pressure changes elicited from the nucleus raphe obscurus. Moreover, we suggest that the glutamate-induced hypertension may be due to the activation of NMDA ionotropic receptor subtypes and the metabotropic receptors may influence this activation through a reduction of excitability at level of synapses.
...
PMID:Opposing effects on blood pressure following the activation of metabotropic and ionotropic glutamate receptors in raphe obscurus in the anaesthetized rat. 869 85

It has been proposed that central cholinergic neurons may actively participate in blood pressure control and other cardiovascular regulations. The present study was performed to investigate the role of the glutamate receptors in the regulation of acetylcholine release in rat central nervous system in vitro. In the Mg2+-free condition, L-glutamate, an endogenous ligand for glutamate receptors, elicited [3H]acetylcholine release from striatal slices of Sprague-Dawley rats in a dose-related fashion. Glycine, an allosteric agonist for the N-methyl-D-aspartate type of glutamate receptor, significantly potentiated the increase in [3H]acetylcholine release evoked by L-glutamate. A non-competitive N-methyl-D-aspartate receptor antagonist, MK-801, blocked the L-glutamate-induced increase in [3H]acetylcholine release, although MK-801 had no effects on its own. In spontaneously hypertensive rats, the facilitatory effect of L-glutamate on [3H]acetylcholine release was significantly smaller than that in Wistar-Kyoto rats. Moreover, L-glutamate in combination with glycine increased the release of [3H]acetylcholine to a lesser extent in SHR than in WKY rats. These results show that L-glutamate increased acetylcholine release from rat striatum, which was highly dependent on the N-methyl-D-aspartate type of glutamate receptor. Furthermore, the lesser facilitation of acetylcholine release by L-glutamate in spontaneously hypertensive rats suggests that the excitatory amino acid may be, at least in part, involved in the regulation of central cholinergic nerve activity in hypertension.
...
PMID:Glutamatergic regulation of [3H]acetylcholine release in striatal slices of normotensive and spontaneously hypertensive rats. 888 81

We have recently reported that the cardiovascular responses to excitatory amino acids are augmented in the rostral ventrolateral medulla of spontaneously hypertensive rats (SHR). In the present study, we investigated whether the responsiveness to excitatory amino acids would be normalized by antihypertensive treatment. Thus we treated 4-week-old SHR and age-matched Wistar-Kyoto (WKY) rats with either enalapril (25 mg/kg per day in drinking water) or vehicle for 8 weeks. At 12 weeks of age, systolic blood pressure in the untreated SHR (248+/-9 mm Hg) was significantly (P<.01) higher than that in the enalapril-treated SHR (140+/-4 mm Hg), untreated WKY rats (148+/-4 mm Hg), and enalapril-treated WKY rats (117+/-1 mm Hg). The pressor responses to L-glutamate (2 nmol) microinjected into the rostral ventrolateral medulla were similar in enalapril-treated and untreated SHR (40+/-5 and 47+/-3 mm Hg, respectively, NS), and these responses were significantly greater than that seen in the untreated WKY rats (24+/-2 mm Hg, P<.01). On the other hand, the pressor response to either N-methyl-D-aspartate, an ionotropic glutamate receptor agonist, or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a metabotropic glutamate receptor agonist, in the enalapril-treated SHR was slightly but significantly smaller than that in the untreated SHR but was still markedly greater than those in untreated and enalapril-treated WKY rats. These results suggest that the augmented responsiveness to excitatory amino acids in the rostral ventrolateral medulla of SHR may be at least partly genetically determined and cannot be normalized by the treatment with enalapril.
Hypertension 1998 Jan
PMID:Antihypertensive treatment and the responsiveness to glutamate in ventrolateral medulla. 944 94


1 2 3 4 Next >>

---