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)

We investigated the role of glutamatergic synapses in the expression of Fos protein at the nucleus tractus solitarii following baroreceptor activation in rats anaesthetized with pentobarbital sodium. Microinjection of L-glutamate (1 nmol) bilaterally into the nucleus tractus solitarii elicited significant hypotension and bradycardia. There was a concurrent increase, as determined immunohistochemically, in the expression of Fos protein at the commissural, medial and dorsomedial subnuclei of the caudal nucleus tractus solitarii. These effects were blunted when L-glutamate was co-administered with either the selective N-methyl-D-aspartate or non-N-methyl-D-aspartate glutamate receptor antagonist, dizocilpine maleate (200 pmol) or 6-cyano-7-nitroquinoxaline-2,3-dione (8 pmol), into the caudal nucleus tractus solitarii. Repeated and scheduled transient hypertension evoked by phenylephrine (2.5, 5.0 or 10.0 microg/kg, i.v.) also appreciably increased the number of Fos-immunoreactive neurons at the commissural, medial and dorsomedial subnuclei of the caudal nucleus tractus solitarii. The expression of Fos protein in this fashion was reduced, simultaneous with a discernible depression in baroreceptor reflex response, when baroreceptor activation was coupled with microinjection bilaterally of dizocilpine maleate (200 pmol) or 6-cyano-7-nitroquinoxaline-2,3-dione (8 pmol) into the nucleus tractus solitarii. Regression analysis showed that the depressive action on the baroreceptor reflex response by both glutamate receptor antagonists correlated positively to the reduction in Fos-immunoreactivity in the nucleus tractus solitarii after baroreceptor activation. Double immunohistochemical staining revealed that nucleus tractus solitarii neurons that showed Fos immunoreactivity were generally also immunoreactive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunit 1. On the other hand, Fos immunoreactivity was usually absent from neurons in the nucleus tractus solitarii that were immunoreactive to N-methyl-D-aspartate receptor subunit 1. These results suggest that glutamatergic neurotransmission plays an active role, via comparable contributions from both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors, in the expression of Fos protein at the caudal nucleus tractus solitarii in response to baroreceptor activation.
...
PMID:Mediation by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors in the expression of Fos protein at the nucleus tractus solitarii in response to baroreceptor activation in the rat. 946 1

An antisense oligodeoxynucleotide which specifically blocked the production of the glutamate receptor subtype NMDAR1 was administered to the nucleus tractus solitarius (NTS) in order to examine the role of this receptor in baroreflex control of heart rate. Baseline blood pressure and heart rate were unchanged by NTS treatment with the antisense oligodeoxynucleotide to the NMDAR1 receptor subunit. However, the reflex bradycardia evoked in response to the hypertension induced by bolus administration of phenylephrine was significantly attenuated following bilateral NTS antisense oligodeoxynucleotide treatment. Administration of the corresponding mismatched antisense oligodeoxynucleotide did not significantly alter the reflex bradycardia. These data indicate that NMDAR1 receptors are involved in neurotransmission in the baroreflex arc at the level of the NTS. The specificity of antisense oligodeoxynucleotides may prove to be a useful technique to analyze the role of receptor subtypes mediating neurotransmission in central pathways.
...
PMID:Modulation of arterial baroreflexes by antisense oligodeoxynucleotides to NMDAR1 receptors in the nucleus tractus solitarius. 991 25

The rostral ventrolateral medulla (RVLM) is considered a major center for the regulation of sympathetic and cardiovascular activities. Several clinical studies have indicated a possible causal relationship between neurovascular contact of the left RVLM and essential hypertension, and some investigators have suggested that the left RVLM is more sensitive to pulsatile compression than the right RVLM. Previously, we reported that pulsatile compression of the RVLM elevates arterial pressure by enhancing sympathetic outflow in rats; however, we have not investigated the laterality of the responses to the compression. In addition, it remains to be elucidated whether RVLM neurons are activated by compression and, if so, how they are activated. Therefore, we performed compression experiments in rats to investigate these issues. Pulsatile compression was performed on the unilateral RVLM with a pulsating probe in anesthetized and artificially ventilated rats. Pulsatile compression of the unilateral RVLM increased arterial pressure, heart rate, and sympathetic nerve activity. The pressor response to compression was inhibited significantly after local microinjection of glutamate receptor antagonists. Pulsatile compression of the RVLM increased Fos immunoreactivitiy, a marker of neuronal activation, within the nuclei of postsynaptic RVLM neurons. All results were observed symmetrically. The data indicate that the responses to pulsatile compression of the unilateral RVLM are similar on both sides. They also suggest that pulsatile compression of the RVLM increases sympathetic and cardiovascular activities by activating postsynaptic RVLM neurons through the stimulation of the local glutamate receptors in rats.
Hypertension 1999 May
PMID:Pressor response to compression of the ventrolateral medulla mediated by glutamate receptors. 1140 4

Angiotensin II type 1 (AT(1)) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT(1) receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the gamma-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by approximately 40% to 50%) after microinjection of the specific AT(1) receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT(1) receptors.
Hypertension 1999 Dec
PMID:AT(1) receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus. 1060 Nov 34

Whereas induction of the 70-kDa heat shock protein (HSP70) in the nucleus tractus solitarii (NTS), the terminal site in the brain stem for primary baroreceptor afferents, augments baroreceptor reflex (BRR) response, the underlying cellular and molecular mechanism is essentially unexplored. In Sprague-Dawley rats, we evaluated the hypothesis that HSP70 may potentiate BRR response by up-regulating the molecular synthesis and functional expression of glutamate receptors in the NTS. Animals subjected to brief hyperthermic heat shock (HS; 42 degrees C for 15 min) exhibited augmented expression of NR1 or NR2A subunit of N-methyl-D-aspartate (NMDA) receptors, GluR1 or GluR4 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and KA1 subunit of kainate receptors in the NTS. Intriguingly, this up-regulation of glutamate receptors was preceded by an increase in HSP70 expression at the NTS. The HS-induced augmentation in responsiveness of barosensitive NTS neurons to transient hypertension or potentiation of BRR response was discernibly blunted by MK-801 or 6-cyano-7-nitroquinoxaline-2,3-dione. Bilateral microinjection into the NTS of an antisense hsp70 oligonucleotide (50 pmol) before HS significantly suppressed the induced expression of HSP70 or the increase in glutamate receptor subunits in the dorsal medulla and discernibly attenuated the potentiation of BRR response. Control microinjection into the NTS of sense or scrambled hsp70 oligonucleotide (50 pmol) was ineffective. These findings suggest that HSP70 induced by HS may enhance BRR response by up-regulating the molecular synthesis and functional expression of NR1 or NR2A subunit of NMDA receptors and GluR1, GluR4, or KA1 subunit of non-NMDA receptors in the NTS.
...
PMID:Up-regulation of glutamate receptors in nucleus tractus solitarii underlies potentiation of baroreceptor reflex by heat shock protein 70. 1196 Nov 27

The dorsomedial hypothalamus (DMH) is critically implicated in the cardiovascular response to emotional stress. This study aimed to determine whether the DMH is also important in cardiovascular arousal associated with appetitive feeding behavior and, if so, whether locally released angiotensin II and glutamate are important in this arousal. Emotional (air-jet) stress and feeding elicited similar tachycardic (+51 and +45 beats/min, respectively) and pressor (+16 and +9 mmHg, respectively) responses in conscious rabbits. Bilateral microinjection of GABA(A) agonist muscimol (500 pmol) into the DMH, but not nearby hypothalamic regions, attenuated pressor and tachycardic responses to air-jet by 56-63% and evoked anorexia. Conversely, stimulation of the DMH with the glutamate analog kainic acid (250 pmol) elicited hypertension (+25 mmHg) and tachycardia (+114 beats/min) and activated feeding behavior. Local microinjection of a glutamate receptor antagonist, kynurenic acid (10 nmol), decreased pressor responses to stress and eating by 46 and 72%, respectively, without affecting feeding behavior. Bilateral microinjection of a selective AT(1)-receptor antagonist, candesartan (500 pmol), into the DMH, but not nearby sites, attenuated pressor and tachycardic stress responses by 31 and 33%, respectively. Candesartan did not alter feeding behavior or circulatory response to feeding. These results indicate that, in addition to its role in mediating stress responses, the DMH may be important in regulating cardiovascular arousal associated with feeding. Local glutamatergic inputs appear to regulate cardiovascular response to both stress and feeding. Conversely, angiotensin II, acting via AT1 receptors, may selectively modulate, in the DMH, cardiovascular response to stress, but not feeding.
...
PMID:Angiotensin II in dorsomedial hypothalamus modulates cardiovascular arousal caused by stress but not feeding in rabbits. 1614 7

Chukmesundan (CMSD) is composed of 8 medicinal herbs including Panex ginseng C.A. MEYER, Atractylodes macrocephala KOID, Poria cocos WOLF, Pinellia ternata BREIT, Brassica alba BOISS, Aconitum carmichaeli DEBX, Cynanchum atratum BGE, and Cuscuta chinensis LAM and used for the treatment of various symptoms accompanying hypertension and cerebrovascular disorders. This study was carried out to examine the effects of CMSD on N-methyl-D-aspartate (NMDA)-evoked, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-evoked nitric oxide synthase (NOS) activity in mouse brain. In adult forebrain, CMSD influences neuronal maintenance and is neuroprotective in several injury models through mechanisms that are incompletely understood. Interaction is observed between CMSD and nitric oxide (NO). Because NO affects both neural plasticity and degeneration, we hypothesized that CMSD might rapidly modulate NO production. Using in vivo microdialysis we measured conversion of L-[14C] arginine to L-[14C] citrulline as an accurate reflection of NOS activity in adult mouse hippocampus. CMSD significantly reduced NOS activities to 62% of basal levels within 2 days of onset of delivery and maintained NOS activity at less than 45% of baseline throughout 3 days of delivery. These effects did not occur with control (distilled water) and were not mediated by effect of CMSD on glutamate levels. In addition, simultaneous delivery of CMSD treatment prevented significant increases in NOS activity triggered by the glutamate receptor agonists NMDA and AMPA. Rapid suppression by CMSD of basal and glutamate-stimulated NOS activity may regulate neuromodulatory functions of NO or protect neurons from NO toxicity and suggests a novel mechanism for rapidly mediating functions of CMSD. It is shown that NMDA receptor stimulation leads to activation of p21ras (Ras) through generation of NO via neuronal NOS. The competitive NOS inhibitor, L-nitroarginine methyl ester, and CMSD prevents Ras activation elicited by NMDA, thus supporting the physiologic relevance of endogenous NO regulation of Ras. These results suggest that Ras is a physiologic target of endogenously produced NO and indicates a signaling pathway for NMDA receptor activation that may be important for long-lasting neuronal responses.
...
PMID:Neuroprotective effect of Chuk-Me-Sun-Dan on NMDA- and AMPA-evoked nitric oxide synthase activity in mouse brain. 1623 59

Intracerebral hemorrhage (ICH), which constitutes 10 to 15% of all strokes and affects approximately 65,000 people each year in the United States, has the highest mortality rate of all stroke subtypes. Hypertension, cerebral amyloid angiopathy, and anticoagulation underlie the majority of cases of ICH. Warfarin not only increases the risk but also increases the severity of ICH by causing hematoma expansion. With the advent of gradient-echo magnetic resonance imaging, patients with underlying cerebral amyloid angiopathy or hypertensive vasculopathy can be identified, and measures can be taken to prevent ICH. Initiating an antihypertensive regimen in a patient with nonlobar microbleeds suggestive of hypertensive vasculopathy, and withholding warfarin in patients with lobar microbleeds suggestive of cerebral amyloid angiopathy, are emerging prevention strategies. Although a treatment for cerebral amyloid angiopathy does not exist, agents targeting beta-amyloid metabolism and bioactivity are promising candidates. Strategies for preventing warfarin-associated hemorrhage include strict monitoring of anticoagulation levels and using agents such as direct thrombin inhibitors. The future of ICH management lies in therapies targeted at the pathophysiological steps in ICH. Potential treatments include glutamate receptor antagonists for preventing glutamate excitotoxicity, matrix metalloproteinase and thrombin inhibitors for preventing perihematomal edema, and recombinant activated factor VII for preventing hematomal expansion.
...
PMID:Treatment and prevention of primary intracerebral hemorrhage. 1634

An elevation in plasma osmolality elicits a complex neurohumoral response, including an activation of the sympathetic nervous system and an increase in arterial pressure. Using a combination of in vivo and in situ rat preparations, we sought to investigate whether hypothalamic vasopressinergic spinally projecting neurones are activated during increases in plasma osmolality to elicit sympathoexcitation. Hypertonic saline (HS, i.v. bolus), which produced a physiological increase in plasma osmolality to 299 +/- 1 mosmol (kg water)(-1), elicited an immediate increase in mean arterial pressure (MAP) (from 101 +/- 1 to 121 +/- 3 mmHg) in vivo. Pre-treatment with prazosin reversed the HS-induced pressor response to a hypotensive response (from 121 +/- 3 to 68 +/- 2 mmHg), indicating significant activation of the sympathetic nervous system. In an in situ arterially perfused decorticate rat preparation, hyperosmotic perfusate consisted of either 135 mm NaCl, or a non-NaCl osmolyte, mannitol (0.5%); both increased lumbar sympathetic nerve activity (LSNA) by 32 +/- 5% (NaCl) and 21 +/- 1% (mannitol), which was attenuated after precollicular transection (7 +/- 3% and 1 +/- 1%, respectively). Remaining experiments used the NaCl hyperosmotic stimulus. In separate preparations the hyperosmotic-induced sympathoexcitation (21 +/- 2%) was also significantly attenuated after transection of the circumventricular organs (2 +/- 1%). Either isoguvacine (a GABA(A) receptor agonist) or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) microinjected bilaterally into the paraventricular nucleus (PVN) attenuated the increase in LSNA induced by the hyperosmotic stimulus (control: 25 +/- 2%; after isoguvacine: 7 +/- 2%; after kynurenic: 8 +/- 3%). Intrathecal injection of a V(1a) receptor antagonist also reduced the increase in LSNA elicited by the hyperosmotic stimulus (control: 29 +/- 6%; after blocker: 4 +/- 1%). These results suggest that a physiological hyperosmotic stimulus produces sympathetically mediated hypertension in conscious rats. These data are substantiated by the in situ decorticate preparation in which sympathoexcitation was also evoked by comparable hyperosmotic stimulation. Our findings demonstrate the importance of vasopressin acting on spinal V(1a) receptors for mediating sympathoexcitatory response to acute salt loading.
...
PMID:A spinal vasopressinergic mechanism mediates hyperosmolality-induced sympathoexcitation. 1687 4

Exposure of experimental animals to noxious somatic stimulations sometimes induces sustained hypertension. Information regarding the medullary projections of somatic afferents and the neurotransmitters involved in them is incomplete. The present investigation in urethane-anesthetized, artificially ventilated, adult male Wistar rats was undertaken to clarify some of these issues. It was observed that the inhibition of contralateral, ipsilateral, or bilateral rostral ventrolateral medullary pressor area (RVLM) with muscimol attenuated the pressor and tachycardic responses to sciatic nerve stimulation. Similar inhibition of the medial subnucleus of the solitary tract (mNTS) exaggerated the cardiovascular responses to sciatic nerve stimulation. Interruption of the baroreflex by microinjections of ionotropic glutamate receptor antagonists into the mNTS or barodenervation also exaggerated the responses to sciatic nerve stimulation. Unilateral stimulation of the aortic nerve blocked the cardiovascular responses to the sciatic nerve stimulation. These results indicated that in the rat, the ascending afferents in the sciatic nerve project bilaterally to the RVLM as well as mNTS; an excitatory amino acid, probably glutamate, is released in the mNTS in response to the sciatic nerve stimulation; and barodenervation or blockade of baroreflex in the mNTS exaggerates, while baroreceptor stimulation inhibits, cardiovascular responses to somatosensory stimulation.
...
PMID:Cardiovascular responses to somatosensory stimulation and their modulation by baroreflex mechanisms. 1772 57


<< Previous 1 2 3 4 Next >>

---