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)

Effects of intracerebroventricular (third ventricle) injection of N-methyl-D-aspartate (NMDA) on arterial blood pressure, on heart rate, on arginine vasopressin (AVP) and levels of catecholamines in plasma and on the behaviour of normotensive freely-moving rats have been evaluated. N-Methyl-D-aspartate significantly (P less than 0.01) increased arterial blood pressure and levels of catecholamines and AVP in plasma. With 0.1-1.0 micrograms/rat all animals presented psychomotor agitation, stereotyped movements, hyperexcitability, exophthalmus, dyspnoea, jumping, rearing and teething. The selective antagonist for NMDA receptors, 2-APV injected in the third ventricle, significantly (P less than 0.01) antagonized the hypertension, the increase in levels of catecholamines and AVP in plasma and behavioural effects. An antagonist of alpha 1 adrenergic receptors, prazosin (i.v.), an agonist of alpha 2 adrenergic receptors, clonidine (i.c.v.) and a relatively selective antagonist of V1 subtype of receptor of AVP, CGP 25838 (i.c.v. and i.v.), 15 min before NMDA, significantly (P less than 0.01) decreased the effects induced by the injections of NMDA. On the contrary, an antagonist of opiate receptors, naloxone (i.v.), 15 min before NMDA, significantly (P less than 0.01) increased the NMDA-induced modifications. Pretreatment with the antagonists at these doses, did not significantly modify the basal values of arterial blood pressure and behaviour. Only 2-APV sometimes induced ataxia, lasting about 5 min. This study points out an increase in the central sympathetic efferent activity and in release of AVP involved in the NMDA-induced cardiovascular and behavioural effects.
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PMID:Participation of arginine vasopressin-mediated and adrenergic system-mediated mechanisms in the hypertension induced by intracerebroventricular administration of NMDA in freely moving rats. 135 1

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.
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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

N-Methyl-D-aspartic acid (NMDA) (10 pmol in 100 nl of 0.9% sodium chloride solution) was microinjected into the nucleus tractus solitarii (NTS) of urethane-anesthetized, paralyzed and artificially ventilated rats, and cerebral blood flow (CBF) was determined using a combination of labeled microspheres. Moderate hypertension within the upper limit of cerebral autoregulation was induced by blood transfusion in order to measure CBF at normotension. Arterial blood pressure (ABP) was decreased by unilateral microinjection into the NTS in these rats but remained within normotensive range. The CBF in the cerebral cortex ipsilateral to the stimulated NTS significantly (P < 0.01) decreased from 38 +/- 4 (mean +/- S.E.M) to 27 +/- 4 ml.min-1.(100 g)-1(n = 9). The cerebrovascular resistance (CVR) in the cerebral cortex ipsilateral to the stimulated NTS significantly (P < 0.01) increased from 2.6 +/- 0.3 to 4.1 +/- 0.7 mmHg per [ml.min-1.(100 g)-1]. Blockade of NMDA receptors in the NTS with D,L-2-amino-5-phosphonovalerate (AP5, 500 pmol) abolished the CBF decrease and CVR increase responses elicited by microinjection of NMDA into the NTS (n = 9). Blockade of non-NMDA receptors in the NTS with 6,7-dinitro-quinoxaline-2,3-dione (DNQX, 100 pmol) had little effect on the CBF decrease and CVR increase responses elicited by microinjection of NMDA into the NTS (n = 10). Microinjection of the vehicle solution into the NTS had no effects on cerebral circulation (n = 7). Cerebral autoregulation was well maintained at moderate hypertension induced by blood transfusion and at normotension returned from moderate hypertension following controlled hemorrhage (n = 8). These results suggest that the NMDA receptors in the NTS may be involved in the control of cerebral circulation.
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PMID:Effects of microinjection of N-methyl-D-aspartic acid into the nucleus tractus solitarii on cerebral blood flow in anesthetized rats. 780 68

At the acute stage of cerebral ischemia, the "therapeutic window" probably does not last more than 6-12 hours. Despite similar treatments, patients admitted in stroke specialist units are more likely to survive and to have a good functional outcome than patients treated in general wards. In most cases acute arterial hypertension should not be treated. Thrombolytic agents given within 6 hours after onset, are now under evaluation in several clinical trials. There is no scientific evidence to support the use of anti-coagulation as a curative treatment of acute cerebral ischemia; however, clinical trials remain necessary, especially in progressing stroke. Neuroprotective drugs protect neurons against the consequences of hypoxia in animals: most clinical trials with oral nimodipine led to negative results but the meta-analysis suggests that patients receiving nimodipine within 12 hours after stroke onset might have a lower mortality rate and a better functional outcome. Other clinical trials with neuroprotective drugs are currently running: anti-NMDA drugs, chlomethiazol, tirilazad, ganglioside GM 1, etc Most therapeutic agents are now under evaluation. An early admission of patients with acute stroke is required to evaluate therapeutics agents which probably cannot be effective if started more than 6-12 hours after stroke onset.
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PMID:[Treatment of cerebral ischemia in its acute phase and prospectives]. 805 63

The periaqueductal gray (PAG) area seems to play an important role in modulating several biological functions such as the triggering of stereotyped defence and reproductive behaviour, pain, anxiety and cardiovascular and respiratory activities. Anatomically this midbrain area is made up of symmetric neuronal columns arranged along the long axis of the aqueduct. In this paper we review the most important findings of the last 10-15 years about the interaction between the PAG area and the cardiovascular function. It is shown that these neuronal columns within the PAG area exhibit a viscerotropic organization which elicits both hypertensive and hypotensive responses. In particular, the stimulation of the ventral neuronal column evokes a hypotensive response associated with a regional decrease in the vascular resistance. On the contrary, the stimulation of the dorsal and lateral neuronal columns evokes arterial hypertension associated with specific changes of the vascular resistance. Recently the authors demonstrated that the glutamergic system in the PAG area (prevalently through NMDA subtype receptor) may also be involved in the control of cardiovascular system. Moreover, the involvement of the arginine vasopressin neuropeptide in the hypertension induced by administration of excitatory amino acids into the PAG area has been demonstrated.
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PMID:Periaqueductal gray area and cardiovascular function. 820 41

The effects of acute hyperglycaemia and streptozotocin-induced diabetes on infarct size were measured 48 h after middle cerebral artery occlusion (MCAO) in Fischer 344 rats. Both hyperglycaemia (+46%) and diabetes (+68%) increased infarct volume when compared to normoglycaemic rats. Insulin-treated diabetic rats exhibited an infarct size similar to that observed in normoglycaemic rats. Neuroprotection has been difficult to demonstrate in pathological conditions that increase infarct volume such as chronic arterial hypertension. However, administration of the non-competitive NMDA antagonist, dizocilpine (MK-801), after MCAO, reduced the volume of ischaemic damage (by 33-48%) in all groups. The present findings indicate (a) that the detrimental effects of experimental diabetes on infarct volume are largely attributed to hyperglycaemia; and (b) dizocilpine was as neuroprotective in hyperglycaemia and diabetic conditions as in normoglycaemic rats.
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PMID:Neuroprotection after focal cerebral ischaemia in hyperglycaemic and diabetic rats. 854 55

Microinjections, into the dorso-lateral periaqueductal gray matter, of N-methyl-D-aspartic acid (NMDA, 0.07-7 nmol/rat) significantly (P < 0.01) increased arterial blood pressure in a dose-related manner. Pretreatment, 5 min before NMDA (7 nmol/rat), in the same area with 2-amino-5-phosphonovaleric acid (2-APV, 5 nmol/rat), a selective antagonist of NMDA receptors, significantly (P < 0.01) reduced NMDA-induced arterial hypertension. trans-(+/-)-1-Amino-1,3-cyclopentanedicarboxylic acid (t-ACPD, 6-30 nmol/rat), an agonist of metabotropic glutamate receptors (mGlu receptors), significantly (P < 0.01) decreased arterial blood pressure when microinjected into the dorsal-lateral periaqueductal gray matter. Pretreatment, 5 min before t-ACPD (30 nmol/rat), in the same area with L-2-amino-3-phosphono-propionate (L-AP-3, 30 nmol/rat), a putative antagonist of the mGlu receptors, was not able to prevent t-ACPD-induced hypotension. Microinjections of L-AP-3 (30 nmol/rat) induced a hypotension similar to the one obtained with t-ACPD at the dose of 6 nmol/rat. From these data we can suggest that mGlu receptors act inversely to the NMDA receptors in the dorso-lateral periaqueductal gray area and that L-AP-3 is a partial agonist rather than an antagonist of mGlu receptors within the periaqueductal gray area.
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PMID:Metabotropic and ionotropic glutamate receptors mediate opposite effects on periaqueductal gray matter. 856 29

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.
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PMID:Opposing effects on blood pressure following the activation of metabotropic and ionotropic glutamate receptors in raphe obscurus in the anaesthetized rat. 869 85

We assessed the pressor and sympathetic responses to microinjection of excitatory amino acids (EAA) into the rostral ventrolateral medulla (RVLM) to see whether the response would be augmented in salt-induced hypertension. Seven-week-old Dahl-Iwai salt-sensitive rats were fed either a high- (8%, n = 10) or a low- (0.3%, n = 12) salt diet for 3 weeks. Then, L-glutamate (2 nmol), N-methyl-D-aspartate (NMDA; ionotropic EAA receptor agonist, 20 pmol) or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD; metabotropic EAA receptor agonist, 1 nmol] was microinjected into the RVLM of urethane-anesthetized, artifically ventilated rats. The rats fed a high-salt diet showed a significantly (P < 0.001) higher mean arterial pressure (123 +/- 3 mmHg) than those fed a low-salt diet (99 +/- 2 mmHg). We found similar increases in mean arterial pressure and splanchnic sympathetic nerve activity elicited by microinjection of L-glutamate into the RVLM in the high- (33 +/- 2 mmHg and 52 +/- 10%) and low- (35 +/- 3 mmHg and 46 +/- 8%) salt groups. Similarly, pressor and sympathoexcitatory responses to either NMDA or (1S,3R)-ACPD did not differ between the groups. Microinjections of the lower doses of L-glutamate, NMDA and (1S,3R)-ACPD also showed comparable pressor responses between the groups. These results indicate that salt-induced hypertension in Dahl salt-sensitive rats is not associated with enhanced responsiveness of the RVLM to EAA. This is in contrast with our previous findings that pressor and sympathetic responses to EAA are enhanced in spontaneously hypertensive rats.
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PMID:Pressor and sympathetic responses to excitatory amino acids are not augmented in the ventrolateral medulla of Dahl salt-sensitive rats. 909 45

Although peripheral cholinergic neurotransmission has long been known to play a pivotal role in the control of heart rate and blood pressure, recent evidence has suggested that central cholinergic mechanisms may be involved in the genesis of hypertension, anxiety, cardiorespiratory control, and, in particular, the respiratory modulation of heart rate. Yet, the sites, mechanisms, and receptor subtypes involved in the action of nicotine within the central nervous system are controversial. The present study demonstrates that nicotine has at least 3 sites of action to increase the activity of vagal cardiac neurons. Nicotine, but not muscarinic agonists, activates postsynaptic receptors and a depolarizing inward current in vagal cardiac neurons studied with the perforated patch-clamp technique in a visualized brain stem slice. In addition, nicotine acts at different presynaptic and postsynaptic sites to facilitate glutamatergic neurotransmission. Presynaptic nicotinic receptors increase the frequency of transmitter release and are sensitive to block by alpha-bungarotoxin. Nicotine also elicits a previously undescribed augmentation of postsynaptic non-NMDA currents. The presynaptic and postsynaptic receptors may prove to be future targets in the search for agonists to increase vagal cardiac activity and reduce the fatality associated with cardiac hyperexcitability and for antagonists to reduce cardiac vagal activity in pathological conditions associated with abnormally low heart rates and cardiac function such as sudden infant death syndrome.
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PMID:Nicotine enhances presynaptic and postsynaptic glutamatergic neurotransmission to activate cardiac parasympathetic neurons. 985 41


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