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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.
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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

We investigated whether or not the rostral ventrolateral medulla (RVL) participates in maintaining a higher arterial pressure of spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were anesthetized with chloralose, paralyzed with tubocurarine, and artificially ventilated. Chemical excitation of the RVL neurons by microinjection of excitatory amino acids (L-glutamate) elicited a dose-dependent pressor response in both the SHR and WKY groups. The magnitude of increase in the arterial pressure (AP) was similar in both groups, but the present increase of AP was higher in WKY than in SHR. Chemical lesions of the bilateral RVL produced by the microinjection of tetrodotoxin decreased the AP to the spinal level, which was similar in both groups. The results indicate that the RVL functions as the sole sympathetic output of the brain in SHR, and suggest that the RVL neurons may be tonically overactive to maintain hypertension in SHR.
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PMID:Effects of chemical stimulation and lesion of the rostral ventrolateral medulla in spontaneously hypertensive rats. 168 4

The authors have used intracerebral microdialysis to develop a method for routine monitoring of disturbances in brain energy metabolism in patients in the neurosurgical intensive care unit. Microdialysis was conducted for periods ranging from 2.3 to 8.3 days in four patients (three with severe head injuries and one with severe subarachnoid hemorrhage). Altogether, 4447 chemical analyses from 587 dialysis samples were carried out. Concentrations of the energy-related metabolites lactate, pyruvate, and hypoxanthine were measured, and the lactate:pyruvate ratio was calculated. In addition, the acids glutamate, aspartate, taurine, glutamine, asparagine, and glycine were measured in one patient. The microdialysis data were matched with various clinical events, including intracranial hypertension and therapeutic interventions such as initiation or withdrawal of barbiturates and cerebrospinal fluid drainage. The present study shows that microdialysis can be used for long-term measurement of extracellular fluid (ECF) energy-related metabolites and amino acids in the frontal cortex of neurosurgical patients in a clinical setting. Fluctuations of the measured ECF energy-related substances corresponded to various clinical events presumably involving hypoxia/ischemia. The authors found a 25-fold increase in ECF glutamate, aspartate, and taurine under conditions of energy perturbation, as indicated by high levels of the lactate:pyruvate ratio, lactate, and hypoxanthine. The use of long-term intracerebral microdialysis in patients opens a new field of clinical research, with many possibilities for improving insight into intracranial dynamics in acute cerebral conditions.
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PMID:Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis. 172 72

Traumatically induced subtotal hippocampal neuronal loss traditionally has been considered a consequence of intracranial hypertension and impaired cerebral perfusion. We have examined the frequency and distribution of hippocampal lesions in an acceleration model of brain injury in 54 anesthetized nonhuman primates undergoing physiologic monitoring and subjected postinjury to comprehensive neuropathologic examination. Hippocampal lesions occurred in 32/54 animals (59%). These lesions always involved the CA-1 hippocampal subfield and were bilateral in 24 animals. Hippocampal involvement was not associated with marked elevation of intracranial pressure or depression of cerebral perfusion pressure. These lesions occurred in the absence of involvement of other brain regions considered selectively vulnerable to hypoxic insults. Hippocampal damage occurred in 46% of animals with mild injury characterized by brief periods of unconsciousness and no residual neurologic deficit. Ninety-four percent of animals with severe injuries and prolonged posttraumatic coma had hippocampal involvement. Traumatically induced selective neuronal necrosis of the hippocampus is a specific lesion not explained by the conventional mechanistic theories of head injury. An alternative hypothesis, such as excitotoxicity involving glutamate or other neurotransmitters, may account for the lesions demonstrated in this study.
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PMID:Selective vulnerability of hippocampal neurons in acceleration-induced experimental head injury. 180 33

This study was designed to compare the cardiovascular influences of the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM) in young (5-6 weeks) spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. SH and WKY groups had similar pressor and depressor responses to microinjection of L-glutamate into the RVLM and the CVLM, respectively. In addition the results of this study indicate a reduced tonic sympathoinhibitory function of the CVLM in young SH rats, which may contribute to the development of hypertension in the spontaneously hypertensive rat.
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PMID:The rostral and caudal ventrolateral medulla in young spontaneously hypertensive rats. 196 62

In anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, the neurons in the nucleus tractus solitarius (NTS) were chemically stimulated by microinjections of L-glutamate and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (either 57Co, 113Sn and 46Sc or 141Ce, 85Sr and 46Sc). Unilateral chemical stimulation of the NTS (n = 14) decreased CBF significantly in most brain areas. The decrease in CBF was not due to the decrease in arterial blood pressure (ABP) because the CBF of the whole cerebral cortex during the chemical stimulation of the NTS was significantly smaller (P less than 0.05) than the CBF during controlled hemorrhagic hypotension (n = 10). In another group of rats (n = 6), moderate hypertension was induced by blood transfusion. Unilateral chemical stimulation of the NTS in these rats decreased ABP but it remained within normotensive range. A significant (P less than 0.05) decrease in CBF (from 62 +/- 28 (mean +/- S.D.) to 48 +/- 23 ml.min-1.(100 g)-1) and increase in cerebrovascular resistance (from 1.9 +/- 1.2 to 2.6 +/- 1.2 mm Hg per [ml.min-1.(100 g)-1]) was observed in the whole cerebral cortex of these rats. Chemical stimulation of the NTS did not affect the reactivity of the cerebral vessels to hypercapnea (n = 5). These results suggest that the cell bodies within the NTS may play a role in the control of cerebral circulation.
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PMID:Chemical stimulation of the nucleus tractus solitarii decreases cerebral blood flow in anesthetized rats. 197 9

Reports suggested that the predominant site of action for the antihypertensive effects of clonidine is the rostral ventrolateral medulla (RVL), the presumed tonic vasomotor center. This study examined whether clonidine directly interacts with nerve terminal alpha 2-adrenergic receptors in the RVL to inhibit the release of sympathoexcitatory transmitters like glutamate (Glu) and aspartate (Asp), and/or facilitate the release of sympathoinhibitory transmitters like gamma-aminobutyric acid (GABA). Release of GABA and Glu was measured from synaptosomes prepared from the rostral ventral medulla of spontaneously hypertensive rats (SHR), a genetic model of hypertension, and normotensive Wistar-Kyoto rats (WKY). Quantification of neurotransmitter release was performed by high-performance liquid chromatography. Depolarization with 35 mM K+ significantly increased by 58-110% the release of GABA, Glu and Asp; however, no strain differences were observed. In contrast, spontaneous release of GABA and Asp was significantly lower in SHR than that of WKY (-36 and -41%, respectively); this effect was not observed for Glu. Clonidine (1 and 10 microM) enhanced the spontaneous release of GABA (+44%), Asp (+50%) and Glu (+70%) in SHR, but not WKY; this effect was prevented by yohimbine (1 microM). These data, together with previous findings, support the presence of facilitory alpha 2-adrenergic receptors on nerve terminals of GABAergic, glutamatergic and aspartatergic neurons in the rostral ventral medulla. These findings also suggest the existence of another inhibitory transmitter that may mediate the actions of clonidine to decrease sympathetic outflow from the RVL.
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PMID:Evidence for clonidine presynaptically modulating amino acid release in the rostral ventral medulla: role in hypertension. 198 40

To better understand and treat painful conditions, one needs to identify the cause, discover the source, and develop knowledge of peripheral and central pain transmission; headaches are no exception. The development of appropriate animal models is important. Accordingly, we have reviewed the anatomy, neurochemistry, electrophysiology, and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine, cluster, and other headache syndromes in humans. For example, based on recent anatomic dissections, the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology. This plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients. As in other nociceptive systems, trigeminovascular axons assume at least two important roles. One concerns the transmission of nociceptive information. Electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral (vessel) and somatic (forehead) inputs to mediate the referral of vascular pain to superficial tissues. A second important role concerns the initiation of local increases in blood flow and enhanced protein permeability (sterile inflammation) via the axonal release of vasoactive neuropeptides. Plasma extravasation develops within the dura mater following trigeminal stimulation. Extravasation can be blocked by the administration of ergot alkaloids or sumatriptan, a new serotonin-like agonist, and a prejunctional (neuronal) mechanism of action for these drugs (such as blockade of release) was suggested based on experimental evidence. Whether vasoconstriction also relates to the therapeutic efficacy remains to be determined. As in other organ systems, real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers. The stimulus may come from external conditions such as reduced blood flow or hypoglycemia. The brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized (e.g., glutamate-induced neurotoxicity, seizures). Molecules of relevance include bradykinin, prostaglandins, leukotrienes, and potassium. Experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon-reflex like mechanisms. An important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Basic mechanisms in vascular headache. 217 82

Passive or neurogenic hypertension was produced by ligation of the aorta or microinjection of glutamate diethyl ester (GDEE) into the intermediate one-third of the nucleus tractus solitarius (NTS), respectively, in 44 anesthetized, artificially ventilated rats. After bilateral sympathectomy, the blood flow (microsphere method) was increased in the cerebral cortex, thalamus, and mesencephalon in a pressure-dependent manner in the face of neurogenic hypertension, as compared with the flow during passive hypertension. We speculate that some neurogenic mechanism tends to impair cerebrovascular autoregulation when afferents arising from cardiovascular receptors were blocked by GDEE within the NTS.
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PMID:An increase in regional brain blood flow during hypertension induced by chemical inhibition of the nucleus tractus solitarius in rats. 225 67


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