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

Microinjections of N-methyl-D-aspartate (NMDA) into the caudal ventrolateral medulla of the rat led to a decrease in arterial pressure whereas 2-amino-5-phosphonovalerate injected bilaterally into this region produced hypertension and blocked the depressor effect of aortic nerve stimulation. High K+ stimulation via push-pull cannula caused a calcium-dependent release of endogenous glutamate from the region. These results provide evidence for the NMDA receptor system involved in tonic vasodepressor control in the rat caudal ventrolateral medulla.
 ...
PMID:N-methyl-D-aspartate receptors mediate tonic vasodepressor control in the caudal ventrolateral medulla of the rat. 285 14

Dextrorphan HCl (Ro 01-6794/706) is an NMDA receptor antagonist with clinical potential for administration in an elderly population of acute ischemic stroke patients. In vivo experience with such patients demonstrated a consistent pharmacologic effect/adverse experience profile that is typical of an NMDA receptor antagonist (e.g., nystagmus, nausea, vomiting, agitation, somnolence, hallucinations and hypertension). For the most part, these pharmacologic effects were mild to moderate in severity; short-lived; reversible; not life-threatening and subjectively tolerated. The most serious pharmacologic effect produced by dextrorphan administration was hypotension, which occurred within a well-defined window of 90 minutes from the start of the loading dose infusion in patients who received 200 mg/hr or greater loading dose infusions. In all cases it was reversible without neurologic sequelae. Careful review of demographic and pharmacokinetic parameters did not demonstrate any overriding factor(s) to the production of hypotension other than the rate of the loading dose infusion. Severe hypotension, severe decreased levels of consciousness and respiratory depression should not be generally expected at loading doses less than 200 mg/hr. In summary, dextrorphan can be safely given to an elderly population of ischemic stroke patients as a loading dose rate below 200 mg/hr and as a maintenance dose rate between 50-90 mg/hr for 24 hours when patients are monitored carefully for pharmacologic effects.
 ...
PMID:Safety, tolerability and pharmacokinetics of the N-methyl-D-aspartate antagonist Ro-01-6794/706 in patients with acute ischemic stroke. The Dextrorphan Study Group and Hoffmann-La Roche. 748 11

In this study we found that cardiovascular effects were differentially regulated by N-methyl-D-aspartate (NMDA) in the rostral ventral lateral medulla (RVLM) of spontaneously hypertensive rats (SHRs) compared to their normotensive controls (Wistar-Kyoto rats, WKYs). Adult SHRs and WKYs were anesthetized with urethane, cervically vagotomized, and placed in a sterotaxic frame. We found that electrical stimulation or local application of N-methyl-D-aspartate into the RVLM produced hypertension in both strains. Microinjection (3.5-4.0 nmol) of AP5 (2-amino-5-phosphono-valerate), an NMDA receptor antagonist, to the RVLM did not affect resting blood pressure; however, this agent antagonized hypertensive responses evoked by low-frequency electrical stimulation (5-20 Hz) in both strains. The elevation in blood pressure evoked by stimulation at a higher frequency (60 Hz) was not affected by AP5. These results suggest that NMDA receptors are involved in the low frequency, electrically evoked hypertension in both strains. We also found that SHRs had a larger pressor response to microinjection of NMDA and electrical stimulation than did WKYs. AP5 abolished the differences in evoked hypertension between WKYs and SHRs during low-frequency (5-10 Hz) electrical stimulation. These data suggest that the hypersensitivity of RVLM to low-frequency electrical stimulation in SHRs involve NMDA receptors. We previously reported that AP7 antagonizes NMDA and carotid clamping-induced hypertension. In this study, we found that when locally applied to RVLM, AP5 antagonized hypertension evoked by clamping the carotid arteries in SHRs and WKYs. Thus, carotid clamping-induced hypertension may also involve NMDA receptors in the RVLM.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiovascular effects of NMDA in the RVLM of spontaneously hypertensive rats. 762 72

The Milan hypertensive strain (MHS) of rats, in addition to having hypertension, is also characterized by a genetic deficiency in calpastatin, the endogenous inhibitor of calpain. Since this protease has been implicated in long-term potentiation (LTP), we have investigated whether induction of this form of plasticity was altered in this strain of rats as compared to control animals (Milan normotensive strain, MNS). Progressive induction of LTP by increasing numbers of high frequency trains resulted in a greater degree of potentiation measured with all inducing protocols in MHS as compared with MNS animals. This difference was not related to the hypertension, since another hypertensive strain (the SHR strain) and a segregated Milan hypertensive strain, expressing only the hypertension but not the calpastatin deficiency (the MHNE strain), exhibited an LTP indistinguishable from control rats. Treatment of MHNE rats for 2 months with isovalerylcarnitine, a compound that increases calpain activity, also resulted in a greater amount of LTP induced by high frequency trains. These effects were not related to an enhancement of the NMDA receptor dependent component of responses to burst stimulation. These results are consistent with the idea that conditions under which calpain activation is facilitated are associated with a greater degree of synaptic potentiation.
 ...
PMID:A genetic deficiency in calpastatin and isovalerylcarnitine treatment is associated with enhanced hippocampal long-term potentiation. 770 42

In urethane-anesthetized male Sprague-Dawley rats, microinfusion of N-methyl-D-aspartate (NMDA) into the area postrema (AP) at the dose of 10 ng produced significant decreases in mean arterial pressure (MAP) (-26 +/- 5 mmHg), heart rate (HR) (-34 +/- 6 bpm), renal blood flow, mesenteric blood flow, and iliac vascular resistance. In addition, microinfusion of the same dosage of NMDA into the medial nucleus tractus solitarius (mNTS) produced significant decreases in MAP (-33 +/- 4 mmHg), HR (-33 +/- 6 bpm), renal blood flow, mesenteric blood flow and vascular resistance, and iliac blood flow and resistance. MK-801 (dizocilpine) microinfusion alone produced no significant changes in MAP or HR when microinfused either into the AP or unilaterally into the mNTS; however, bilateral microinfusion of MK-801 into mNTS produced sustained hypertension and tachycardia, lasting about 30 min. MK-801 pretreatment at both AP and mNTS effectively blocked NMDA-induced cardiovascular responses. MK-801 microinfusion at AP significantly attenuated baroreceptor reflex-mediated bradycardia elicited by intravenous injection of phenylephrine, but did not alter reflex tachycardia elicited by intravenous nitroprusside. In conclusion, NMDA receptor-mediated neurotransmission is involved in the cardiovascular functions of both AP and mNTS. Both loci appear to be sites of action for MK-801.
 ...
PMID:Cardiovascular effects of NMDA and MK-801 infusion at area postrema and mNTS in rat. 786 99

In the present study the influence of arcaine (0.01-1 microgram/rat), an in vitro putative non-competitive antagonist of the NMDA receptors, on cardiovascular changes induced by intracerebral administration of N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) has been evaluated. Both NMDA and arcaine were microinjected into the periaqueductal gray (PAG) area of anesthetized rats. Arcaine did not decrease NMDA-induced arterial hypertension and tachycardia, but, in a dose-related manner, increased the NMDA-induced cardiovascular effects. Moreover, treatment with arcaine was not able per se to modify arterial blood pressure and heart rate basal values. Although updated in vitro reports indicate arcaine as a blocker of the NMDA receptors by an open channel mechanism, our in vivo results, at the level of the PAG area, show this not to be true. Indeed the drug may facilitate NMDA receptor activation.
 ...
PMID:Evidence that arcaine increases the N-methyl-D-aspartate-induced cardiovascular effects into the periaqueductal gray area of anesthetized rats. 791 17

1. The purpose of this study was to investigate further the role of the excitatory amino acid (EAA) system of neurotransmission, particularly of the NMDA receptor, in the central regulation of cardiac function. 2. Electrical stimulation of the paraventricular nucleus of the hypothalamus (PVN) in pentobarbitone anaesthetized rabbits induced a cardiovascular response mainly characterized by a positive inotropic effect, hypertension and a marked increase in the myocardial oxygen demand index. 3. The intracerebroventricular (i.c.v.) or intravenous (i.v.) injection of different EAA antagonists acting on different sites of the NMDA receptor/channel complex dose-dependently blunted the excitatory cardiovascular effects of PVN stimulation. 4. 5,7 Dichlorokynurenic acid was used as a specific glycine site antagonist and 2-amino-5-phosphonovaleric acid was used to block the agonist recognition site; ketamine was used as a channel blocker site antagonist and ifenprodil as a blocker of the polyamine binding site. 5. 5,7 Dichlorokynurenic acid (125 and 250 micrograms kg-1, i.c.v.) virtually abolished the cardiovascular responses, inducing only haemodynamic depression at the highest dose used. 2-Amino-5-phosphonovaleric acid (0.1 to 1.0 mg kg-1, i.c.v.) elicited a reduction of the peak values observed during PVN stimulation which was accompanied by a decrease of the basal cardiovascular parameters. Ketamine (2.5 and 10 mg kg-1) and ifenprodil (1 mg kg-1), injected intravenously, blocked the haemodynamic response induced by PVN stimulation without marked reduction of the basal haemodynamics. 6. It is concluded that glutamate neurotransmission is not only involved in vasomotor tone control but also in the central control of cardiac function and can therefore modulate the myocardial oxygen demand.
 ...
PMID:Prevention by NMDA receptor antagonists of the centrally-evoked increases of cardiac inotropic responses in rabbits. 791 76

We investigated the effect of the polyamine spermidine (SPD) (0.01-1 microgram/rat) on hypertension induced by N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) microinjected into the latero-caudal periaqueductal gray (PAG) area of freely moving rats. Pretreatment with a low dose of SPD (0.01 microgram/rat) significantly increased NMDA-induced hypertension. On the contrary, higher doses of SPD (0.1 and 1 microgram/rat) significantly decreased NMDA-induced cardiovascular changes. SPD alone did not modify arterial blood pressure. Arcaine (1 microgram/rat), a putative antagonist at the polyamine recognition site on NMDA receptors, when microinjected into the PAG area, prevented the negative but not the positive modulatory effects of SPD on the NMDA-induced cardiovascular changes. Pretreatment with SPD did not affect cardiovascular effects induced by quisqualic acid (QUIS), a non-NMDA receptor agonist. These data, in agreement with the in vitro results, suggest that at the level of the PAG area, the polyamines also show multiple actions at NMDA receptors in vivo.
 ...
PMID:Effects of the polyamine spermidine on NMDA-induced arterial hypertension in freely moving rats. 793 16

The cardiovascular effects of nanoliter microinfusions of muscimol, bicuculline, and MK-801 (dizocilpine) into area postrema (AP) were tested in urethane-anesthetized male Sprague-Dawley rats. Microinfusion of muscimol (10 nl/min/5min, 1 ng/nl) into the AP produced significant hypertension (+29 +/- 8 mmHg), but no significant change in heart rate (HR). Microinfusion of bicuculline (10 nl/min/5 min, 1 ng/nl) into the AP produced significant hypotension (-27 +/- 4 mmHg) and bradycardia (-53 +/- 10 bpm). Treatment of the AP with MK-801 (20 nl/min/5 min, 6 ng/nl) produced no changes in mean arterial pressure or HR by itself, but it completely blocked the hypotension and bradycardia produced by bicuculline infusion, without affecting the hypertension produced by muscimol microinfusion into AP. Following pretreatment of AP with MK-801, microinfusion of muscimol into the AP produced significant tachycardia (+51 +/- 16 bpm). The data suggest that a) GABAergic neurotransmission in the AP affects its cardiovascular functions; b) functional interactions between NMDA receptor-mediated neurotransmission and GABAA receptor-mediated neurotransmission within the AP modulate blood pressure and HR regulation.
 ...
PMID:MK-801 affects cardiovascular responses produced by GABAA agents in area postrema. 795 59

During the last decade, a multitude of experimental arguments have led to the concept that EDRF is nitric oxide (NO), a messenger not only involved in the control of vasomotor tone but also in vascular homeostasis, neuronal and immunological functions. Regardless of its origin, endogenous NO is produced through the conversion of L-arginine to L-citrulline by NO-synthase (NOS) from which several isoforms have recently been isolated, purified and cloned. NOS-type I (isolated from brain) and type III (isolated from endothelial cells) are termed "constitutive-NOS" and produce picomolar levels of NO from which only a small fraction elicits physiological responses. These isoforms are regulated by Ca(2+)-calmodulin with NADPH, FAD/FMN and tetrahydrobiopterin as co-factors and reveal a high degree of homology with the amino-acid sequence of cytochrome P450 reductase within the C-terminal domain. Functionally, neuronal-NOS type I is important in neurotransmission (modulation of NMDA receptor), the central control of vascular homeostasis and possibly learning and memory. In the peripheral nervous system, NOS appears to be linked to nonadrenergic noncholinergic (NANC) neuronal pathways. Endothelial-NOS type III is essential for the control of vascular tone in response to the release of endogenous mediators, although shear stress is the major trigger of endothelial-NOS activity under physiological conditions. NOS-type III also contributes to the prevention of abnormal platelet aggregation. NOS-types II and IV (isolated from macrophages) are Ca(2+)-calmodulin independent and are termed "inducible-NOS" since their activation is only promoted under pathophysiological situations where macrophages exert cytotoxic effects in response to cytokines. In contrast with NOS-types I and III, activation of NOS-type II in these cells induces the formation of nanomolar levels of NO which act as a defense mechanism of the immune system. Dysfunctions of the L-arginine-NO pathway have been characterized in multiple diseases (atherosclerosis, hypertension, diabetes, sepsis, cerebral ischemia, etc) and the design of more selective activators/inhibitors of NOS isoforms is a new challenge for the understanding of their pathophysiology and treatment.
 ...
PMID:Nitric oxide: an ubiquitous messenger. 829 80


1 2 3 4 5 6 Next >>