UMLS:C0020538 - FACTA Search

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)

The interrelationship between the breakdown of the blood-brain barrier according to the Evans-blue passage and an abrupt increase in blood pressure (DeltaP) was studied in rats subjected to adrenaline-induced acute hypertension and also pentylenetetrazol-induced seizures. Arterial blood pressure was increased by adrenaline, then immediately i.v. nifedipine was injected and subsequently decreased to the control value in the acute hypertensive group. Arterial blood pressure was increased by pentylenetetrazol, then immediately GABA (gamma-aminobutiric acid) was injected and the blood pressure was decreased to the control value in the seizure group. The animals were divided into five groups. Group I: control; Group II: acute hypertension; Group III: acute hypertension + nifedipine; Group IV: seizure; Group V: seizure + GABA. The Evans-blue dye content was found to be 0.25 +/- 0.01 mg% in the whole brain in the control animals, and 0.803 +/- 0.1 mg% in the acute hypertensive group. This difference between these groups was found to be significant: P< 0.01. In the nifedipine group (Group III) the Evans-blue content was 0.30 +/- 0.1 mg% in the whole brain; and there was no significant difference between control values and nifedipine-treated animals (P> 0.5). The Evans-blue content was 1.6 +/- 0.2 mg% in the whole brain during seizure, and decreased to 0.36 +/- 0.1 mg% after GABA injection was administered. There was also no significant difference between the control value and the GABA-treated animals (P> 0.5). These results have shown that an abrupt increase in blood pressure (DeltaP) did not change the blood-brain barrier permeability in both acute hypertension and seizures.
...
PMID:Influence of an abrupt increase in blood pressure on the blood-brain barrier permeability during acute hypertension and epileptic seizures. 1152 87

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. Alterations in the following substances are discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, and corticotropin-releasing factor. Functional changes in these substances occur throughout the hypothalamus but are particularly prominent rostrally; most lead to an increase in sympathetic nervous activity which is responsible for the rise in arterial pressure. A few appear to be depressor compensatory changes. The majority of the hypothalamic changes begin as the pressure rises and are particularly prominent in the young rat; subsequently they tend to fluctuate and overall to diminish with age. It is proposed that, with the possible exception of the Dahl salt-sensitive rat, the hypothalamic changes associated with hypertension are caused by renal and intrathoracic cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a result of renal ischemia and trauma as in the reduced renal mass rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it is submitted, is due to the associated documented impaired ability to excrete sodium. It is proposed, therefore, that the hypothalamic changes in hypertension are a link in an integrated compensatory natriuretic response to the kidney's impaired ability to excrete sodium.
...
PMID:The hypothalamus and hypertension. 1158 98

The effect of blockade of ionotropic GABA and glutamate receptors in the rostral ventrolateral medulla (RVLM) on the relationship between phrenic nerve, splanchnic sympathetic nerve and lumbar sympathetic nerve activities was examined in urethane anesthetized, paralyzed and vagotomized Sprague-Dawley rats. Bilateral microinjection of the GABA-A receptor antagonist, bicuculline (4 mM, 100 nl), into the RVLM dramatically, and almost exclusively, increased the post-inspiratory related discharge in both splanchnic sympathetic nerve and lumbar sympathetic nerve activities and elicited hypertension with fluctuations of arterial pressure phase locked to the discharge of the phrenic nerve. Subsequent bilateral microinjection of kynurenate, a non-selective ionotropic excitatory amino acid receptor antagonist (50 mM, 100 nl), into the RVLM significantly attenuated the sympathoexcitation and hypertension evoked by injection of bicuculline. This was accompanied by an abolition of the post-inspiratory related burst discharge of splanchnic sympathetic nerve and lumbar sympathetic nerve activities. These data suggest that the GABAergic inputs to RVLM tonically inhibit glutamatergic inputs from central respiratory neurons that normally act to increase the firing of presympathetic neurons in the RVLM. Inputs from post-inspiratory neurons appear to be an especially potent excitatory synaptic drive to the presympathetic neurons in the absence of the GABAergic inhibition.
...
PMID:Evidence for a tonic GABA-ergic inhibition of excitatory respiratory-related afferents to presympathetic neurons in the rostral ventrolateral medulla. 1174 95

We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in gamma-amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbetagal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.
Hypertension 2002 Feb
PMID:Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats. 1184 95

Experimental evidence indicates that the hypothalamic paraventricular nucleus modulates sympathetic vasomotor tone and blood pressure and that this modulation is altered in some cardiovascular diseases. This study tested the hypothesis that this nucleus exerts a more significant tonic excitatory modulation of basal sympathetic vasomotor activity in spontaneously hypertensive rats. In anesthetized, artificially-ventilated rats, bilateral microinjections of the GABA(A) receptor agonist, muscimol (1 to 1.5 nmoles per side), into the paraventricular nucleus produced a depressor and sympathoinhibitory response that did not recover. When compared with normotensive rats, this response was more marked in spontaneously hypertensive rats, where lumbar sympathetic nerve discharge was reduced by 75 +/- 3% and mean arterial pressure fell from 119 +/- 7 mm Hg to 58 +/- 3 mm Hg. Blockade of excitatory and inhibitory amino acid receptors in the rostral ventrolateral medulla significantly attenuated this response. Microinjections of small volumes (<20 nL) of GABA were used to localize precisely the responsive region of the paraventricular nucleus. Unilateral injections of GABA into the dorsomedial cap of the paraventricular nucleus induced a brisk depressor (decrease of 42 +/- 4 mm Hg), sympathoinhibitory (decrease by 72 +/- 2%), and bradycardic (decrease of 77 +/- 16 bpm) response. The mechanisms underlying the sympathoinhibition after inactivation of the paraventricular nucleus are not elucidated, but evidence discussed suggests the involvement of a supracollicular sympathoinhibitory pathway. The results presented demonstrate that the paraventricular nucleus exerts a powerful, tonic effect on the control of sympathetic vasomotor tone under basal conditions in anesthetized rats and that this is enhanced in spontaneously hypertensive rats.
Hypertension 2002 Feb
PMID:Inhibition of the hypothalamic paraventricular nucleus in spontaneously hypertensive rats dramatically reduces sympathetic vasomotor tone. 1184 97

Neurons in the commissural nucleus of the solitary tract (commNTS) play an important role in certain cardiovascular responses dependent on sympathetic vasoconstrictor activation, including the arterial chemoreceptor reflex. Electrolytic lesions of the commNTS elicit a fall in arterial pressure (AP) in spontaneously hypertensive rats (SHR). To determine whether the latter result 1) arose from elimination of commNTS neuronal activity rather than en passant axons and 2) was accompanied by a reduction in sympathetic nerve activity, we evaluated the effect of inhibition of neurons in the commNTS on basal splanchnic sympathetic nerve activity (SNA), AP, and heart rate (HR) in SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. In chloralose-anesthetized, paralyzed, and artificially ventilated SHR, microinjection of GABA into the commNTS markedly decreased splanchnic SNA, AP, and HR. The reductions in SNA and AP following similar microinjections in WKY and SD rats were significantly less than those in SHR. Our findings suggest that tonically active neurons in the commNTS contribute to the maintenance of SNA and the hypertension in SHR. The level of tonic discharge of these commNTS neurons in normotensive WKY and SD rats may be lower than in SHR.
...
PMID:Inhibition of neurons in commissural nucleus of solitary tract reduces sympathetic nerve activity in SHR. 1195 31

Experiments were conducted to determine whether the medial amygdala could control hemodynamics through the GABA receptor in anesthetized rats. Bicuculline (10-100pmol), a GABA(A) antagonist, injected into the anterior basomedial amygdala (medial amygdala) produced dose-related increases in blood pressure (BP) and heart rate (HR). Following microinjection of a 100pmol dose, plasma norepinephrine and epinephrine also rose significantly. In a group that had undergone bilateral adrenalectomy, the same dose of bicuculline into the same region of the amygdala caused similar increases in BP and HR to those produced in normal rats. Pretreatment with an intraperitoneal injection of hexamethonium prevented these responses. When bicuculline was given intravenously (100pmol) it failed to effect these cardiovascular changes. Bicuculline-induced hypertension and tachycardia were inhibited by microinjection of muscimol, a GABA agonist, into the anterior basomedial amygdala. The results thus demonstrate that the influence of bicuculline on BP and HR is through action on the anterior basomedial amygdala and direct sympathetic outflow to heart and vascular smooth muscle. There is tonic GABAergic inhibition of sympathetic outflow in the medial amygdala that plays a part in regulating hemodynamics in the limbic system.
...
PMID:Role of medial amygdala in controlling hemodynamics via GABA(A) receptor in anesthetized rats. 1199 48

The exact mechanisms by which NO mediates its neuromodulatory effects within the central control of cardiovascular functions are still unclear. Both excitatory and inhibitory actions of NO in different regions of the brainstem have been reported, and that it could be caused by direct actions of NO on neurones and/or by NO-mediated changes in local cerebral blood flow. Microinjection studies suggest that direct modulation of neuronal activity by NO through cyclic 3'-5' guanosine monophosphate (cGMP)-dependent mechanisms predominates. In contrast, endogenous NO produces. only minor changes in local cerebral blood flow, and potentiation of NO-dependent vasodilation with an inhibitor of phosphodiesterase V (PDE5i) has no significant effect on sympathetic activity. Activation of the NO-system in the lower brain stem modulates various central and reflex-activated neuronal pathways. To a large extent, this appears to be mediated by NO-induced GABA- and glutamate-release within the ventrolateral medulla (VLM) and the nucleus of the solitary tract (NTS). In addition, NO has been shown to reduce local generation of angiotensin II (AII) in all areas. Recent studies suggest that the NO-mediated modulation of autonomic function is severely impaired in cardiovascular diseases. Possibly in conjunction with AII, which triggers and promotes superoxide radical generation, chronic oxidative stress (COS) could act as a key mediator of this process. Evidence supporting this hypothesis comes from studies on pigs that were chronically treated with organic nitrates to pharmacologically induce COS. In these animals, microinjection of superoxide dismutase into the rostral VLM (RVLM) diminished sympathetic activity by up to 70%, whereas peroxynitrite, a key mediator of NO-related oxidative stress, had excitotoxic effects. Antagonism of neuronal COS may therefore represent a novel approach to counteract neurohumoral activation in diseases such hypertension, obesity and heart failure.
...
PMID:Mechanisms of action of nitric oxide in the brain stem: role of oxidative stress. 1214 34

Heart failure and hypertension are associated with increases in angiotensin II (ANG II) activity. One brain area where ANG II effects may be particularly important in these situations is the nucleus of the solitary tract (NTS). Located in the dorsomedial medulla, the NTS is the termination site of baroreceptor afferents and is essential for mediating the baroreflex. In hypertensive animals the baroreflex is impaired; this may be reversed by antagonizing ANG II AT1 receptors in the NTS. Recently, we showed that the baroreflex depressant action of ANG II in the NTS is mediated by activation of endothelial nitric oxide synthase (eNOS) and enhanced release of GABA. Using conventional pharmacological tools and a range of adenoviral-mediated expression of dominant negative proteins, we have determined the intracellular pathway(s) in the NTS by which ANG II activates eNOS. Our data indicate that ANG II acting in the NTS depresses the baroreflex via a Gq protein-mediated activation of phospholipase C, which through 1,4,5-inositol triphosphate causes release of calcium from the IP3-sensitive intracellular stores and calcium-calmodulin formation. In contrast, multiple site disruption of a pathway leading to eNOS activation via the serine/threonine kinase Akt was ineffective
...
PMID:Genetic and pharmacological dissection of pathways involved in the angiotensin II-mediated depression of baroreflex function. 1237 82

It is well known that nitric oxide (NO), within the paraventricular nucleus (PVN) of the hypothalamus, mediates sympatho-inhibition via an inhibitory GABA-ergic mechanism. Furthermore, the inhibitory GABA-ergic mechanism is impaired in the spontaneously hypertensive rat (SHR). These data suggest that the NO system, within the PVN, may also be impaired in the SHR. In addition, previous studies have documented that daily exercise attenuates the development of tachycardia, hypertension and blood pressure related cardiovascular disease risk factors in SHR. These data suggest that daily exercise enhances the inhibitory GABA-ergic and/or NO systems. Therefore, this study was designed to test the hypothesis that hypertension, in the SHR, is associated with a lower number of NADPH-diaphorase (a commonly used marker for neuronal NOS activity) positive neurons within the PVN and that daily exercise increases the number of NOS positive neurons. Using a standard histochemical protocol, NOS positive neurons were measured in the PVN, supraoptic nucleus, median preoptic area, lateral hypothalamus, nucleus of the tractus solitarius and rostral ventrolateral medulla. Results document that SHR have significantly fewer NOS-positive neurons in the PVN than their genetic control, the Wistar-Kyoto (WKY) rats (110+/-11 versus 139+/-17). Furthermore, daily exercise increased the number of NOS positive neurons in the SHR to levels seen in the WKY rats. These data demonstrate that hypertension, in the SHR, is associated with a lower number of NOS positive neurons within the PVN and that daily exercise increases the number of NOS positive neurons within the PVN.
...
PMID:Daily exercise normalizes the number of diaphorase (NOS) positive neurons in the hypothalamus of hypertensive rats. 1241 31

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>