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)

Osmotic agents are still the most common treatment for controlling intracranial hypertension (ICH). Mannitol, glycerol, sorbitol, and hypertonic serum saline are the agents currently available. This work was designed to compare mannitol and glycerol in a similar population of brain injured patients, randomly divided into two groups of eight. The following mean day parameters were obtained: number of infusions, hydric balance, mean arterial pressure (MAP), and intracranial pressure (ICP). Cerebral perfusion pressure (CPP) was calculated. Brain computed tomographies (CT) were obtained on arrival, at follow-up whenever justified and at discharge. For comparison of both groups a modified therapeutic intensity level (mTIL) was used. Both agents induced a statistically equally effective decrease on ICP and increase on CPP evaluated at one and two hours post infusion but the mean day mTIL showed a statistically significant difference in favour of glycerol. The possible explanations of this difference are discussed. According to our results mannitol would be most indicated as a bolus to control sudden rises in ICP whereas glycerol would be most indicated as a basal treatment.
 ...
PMID:Osmotherapy for increased intracranial pressure: comparison between mannitol and glycerol. 930 87

We report a 62-year-old man who developed coma and died in a fulminant course. The patient was well until May 1, 1996 when he noted chillness, tenderness in his shoulders, and he went to bed without having his lunch and dinner. In the early morning of May 2, his families found him unresponsive and snoring; he was brought into the ER of our hospital. He had histories of hypertension, gout, and hyperlipidemia since 42 years of the age. On admission, his blood pressure was 120/70, heart rate 102 and regular, and body temperature 36.3 degrees C. His respiration was regular and he was not cyanotic. Low pitch rhonchi was heard in his right lower lung field. Otherwise general physical examination was unremarkable. Neurologic examination revealed that he was somnolent and he was only able to respond to simple questions such as opening eyes and grasping the examiner's hand, but he was unable to respond verbally. The optic discs were flat; the right pupil was slightly larger than the left, but both reacted to light. He showed ptosis on the left side, conjugate deviation of eyes to the left, and right facial paresis. The oculocephalic response and the corneal reflex were present. His right extremities were paralyzed and did not respond to pain Deep tendon reflexes were exaggerated on the right side and the plantar response was extensor on the right. No meningeal signs were present. Laboratory examination revealed the following abnormalities; WBC 18,400/ml, GOT 131 IU/l GPT 50 IU/l, CK616 IU/l, BUN 30 mg/dl, Cr 2.1 mg/ dl, glucose 339 mg/dl, and CRP 27.4 mg/dl. ECG showed sinus tachycardia and ST elevation in II, III and a VF leads and abnormal q waves in I, V5, and V6 leads. Chest X-ray revealed cardiac enlargement but the lung fields were clear. Cranial CT scan revealed low density areas in the left middle cerebral and left posterior cerebral artery territories. The patient was treated with intravenous glycerol infusion and other supportive measures. At 2: 10 AM on May 3, he developed sudden hypotension and cardiopulmonary arrest. He was pronounced dead at 3:45 AM. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had acute myocardial infarction involving the inferior and the true posterior walls and left internal carotid embolism from a mural thrombus. Post mortem examination revealed occlusion of the circumflex branch of the left coronary artery due to atherom plaque rupture and myocardial infarction involving the posterior and the lateral wall with a rupture in the postero-lateral wall. Marked atheromatous changes were seen in the left internal carotid, the middle cerebral and the basilar arteries; the left internal carotid and the middle cerebral arteries were almost occluded by thrombi and blood coagulate. The territories of the left middle cerebral and the occipital arteries were infarcted; but the left thalamic area was spared. The neuropathologist concluded that the infarction was thrombotic origin not an embolic one as the atherosclerotic changes were severe. Cardiac rupture appeared to be the cause of terminal sudden hypotension and cardiopulmonary arrest. It appears likely that a vegetation which had been attached to the aortic valve induced thromboembolic occlusion of the left internal carotid artery which had already been markedly sclerotic by atherosclerosis. It is also possible that the vegetations in the aortic valve came from mural thrombi at the site of acute myocardial infarction, as no bacteria were found in those vegetations.
 ...
PMID:[A 62-year-old man with an acute onset of consciousness disturbances]. 945 48

Abnormal vascular smooth muscle (VSMC) proliferation is a key feature in diabetes-associated atherosclerotic disease. Since nitric oxide inhibits VSMC tone, migration, adhesion, and proliferation, we examined the effects of high glucose on IL-1beta-induced NO release from VSMCs in culture. Confluent smooth muscle cells, preincubated with either 5 mmol/L (mM) or 20 mmol/L (mM) glucose for 48 hours, were stimulated with IL-1beta. Nitrite was measured in the culture medium after 24 hours. IL-1beta-induced a 15-fold increase in NO production in normal glucose medium. Glucose (10 to 30 mmol/L (mM)) significantly reduced the response to IL-1beta. High glucose (20 mmol/L (mM)) inhibited IL-1beta-evoked NO production by approximately 50%. IL-1beta-stimulated [3H] citrulline-forming activity of the nitric oxide synthase (NOS) was also significantly lower in high-glucose-exposed cells, and this was reflected in diminished cellular levels of NOS protein. To assess the role of protein kinase C (PKC), membrane PKC activity was measured, and glucose (20 mmol/L (mM)) significantly increased it. Immunoblotting of the membranes revealed a glucose-induced increase in the PKC betaII isoform. 1,2-Dioctanoyl-glycerol, a PKC activator, mimicked the high-glucose effect on IL-1beta-induced NO release, while staurosporine, a PKC inhibitor, reversed it. The role of calcium in the glucose-mediated inhibition of cytokine-induced NO release was determined by treatment with BAPTA, an intracellular chelator of calcium. BAPTA partially reversed the inhibitory effects of glucose. Increasing intracellular calcium by A23187, an ionophore or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase, significantly decreased IL-1beta-induced NO release and NOS expression. These results indicate that glucose-induced inhibition of IL-1beta-stimulated NO release and NOS expression may be mediated by PKC activation and increased intracellular calcium.
Hypertension 1998 Jan
PMID:Calcium and protein kinase C mediate high-glucose-induced inhibition of inducible nitric oxide synthase in vascular smooth muscle cells. 945 18

Alterations in fatty acids of membrane phospholipids in essential hypertension may account for altered membrane ion transport, elasticity, and contractility properties of hypertensive tissues. To investigate the abnormalities in membrane fatty acids in essential hypertension, the degree of fatty acid unsaturation ([-CH=CH-]/[-CH3]), the average carbon chain length, ratio of glycerol to fatty acyl chains, ratio of phosphatidylcholine to fatty acyl chains, and the ratio of free and acylated cholesterol to fatty acyl chains in fatty acid fractions of membrane phospholipids of aorta, kidney, and heart were determined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats by 1H nuclear magnetic resonance (NMR) spectroscopy. The degrees of fatty acid unsaturation in the aorta and the kidney membranes were significantly lower in SHR than in WKY rats (aorta, 0.53+/-0.01 v 0.63+/-0.01, n = 5, P = .01; kidney, 0.70+/-0.01 v 0.84+/-0.03, n = 10, P = .01). No significant difference could be detected in fatty acid unsaturation in heart membranes between these two strains. For aorta, kidney, and heart membranes, the average carbon chain lengths of fatty acid fractions of membrane phospholipids were significantly shorter for SHR than for WKY rats (aorta, 15.1+/-0.2 v 18.3+/-0.7, n = 5, P = .02; kidney, 14.5+/-0.2 v 16.4+/-0.4, n = 10, P = .01; heart, 17.3+/-0.5 v 18.8+/-0.6, n = 10, P = .05). The lower unsaturated fatty acid content in membrane phospholipids of the aorta and the kidney, with concomitant reduction in average chain length, may arise from increased oxidation of fatty acid double bonds in hypertensive tissues and may account, in part, for the increased aortic stiffness and abnormal kidney function associated with essential hypertension. Whether the lower unsaturated fatty acid content and decreased carbon chain length of phospholipid membranes in the aorta and the kidney are a cause or a consequence of the high blood pressure, however, remains unknown.
 ...
PMID:Alterations in membrane fatty acid unsaturation and chain length in hypertension as observed by 1H NMR spectroscopy. 954 75

1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth muscle cells (VSMC) and stimulates several events that are important for cell proliferation: DNA synthesis, protein synthesis, increase of cell number, immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2. Receptor characterization indicates mitogenic effects of both P2U and P2Y receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1, MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF, bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II, endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine, and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous arteries and veins. 6. The trophic effects on VSMC and the abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of atherosclerosis, neointima-formation after angioplasty, and possibly hypertension.
 ...
PMID:Extracellular ATP: a growth factor for vascular smooth muscle cells. 959 70

Glycerol is a naturally occurring 3-carbon alcohol in the human body. It is the structural backbone of triacylglycerol molecules, and can also be converted to a glycolytic substrate for subsequent metabolism. Serum glycerol concentrations approximate 0.05 mmol/L at rest, and can increase to 0.30 mmol/L during increased lipolysis associated with prolonged exercise or caloric restriction. When glycerol is ingested or infused at doses greater than 1.0 g/kg bodyweight, serum concentrations can increase to approximately 20 mmol/L, resulting in more than a 10 mOsmol/kg increase in serum osmolality. Glycerol infusion and ingestion have been used in research settings for almost 60 years, with widespread clinical use between 1961 and 1980 in the treatment of cerebral oedema resulting from acute ischaemic stroke, intraocular hypertension (glaucoma), intracranial hypertension, postural syncope and improved rehydration during acute gastrointestinal disease. Since 1987, glycerol ingestion with added fluid has been used to increase total body water (glycerol hyperhydration) by up to 700 ml, thereby providing benefits of improved thermoregulation and endurance during exercise or exposure to hot environments. Despite the small number of studies on glycerol hyperhydration and exercise, it appears to be an effective method of improving tolerance to exercise and other heat-related stressors.
 ...
PMID:Glycerol. Biochemistry, pharmacokinetics and clinical and practical applications. 980 72

Cannabinoids, including the endogenous ligand anandamide (arachidonyl ethanolamide), elicit pronounced hypotension in rats via activation of peripherally located CB1 cannabinoid receptors, which have been also implicated in endotoxin (lipopolysaccharide [LPS])-induced hypotension. The present study was designed to test the role of vascular CB1 receptors in cannabinoid- and endotoxin-induced mesenteric vasodilation. In the isolated, buffer-perfused rat mesenteric arterial bed precontracted with phenylephrine, anandamide induced long-lasting (up to 60 minutes) dose-dependent vasodilation (ED50: 79+/-3 nmol; maximal relaxation: 77+/-2%), inhibited by 0.5 to 5.0 micromol/L of the selective CB1 receptor antagonist SR141716A. Low doses of the calcium ionophore ionomycin also caused mesenteric vasodilation inhibited by SR141716A. The metabolically stable analogue R-methanandamide elicited mesenteric vasodilation (ED50: 286+/-29 nmol), whereas the potent synthetic CB1 receptor agonists WIN 55212-2 and HU-210 caused no change in vascular tone or only a minor dilator effect not affected by SR141716A, respectively. The endogenous ligand 2-arachidonyl glycerol caused no change in vascular tone, whereas Delta9-tetrahydrocannabinol and arachidonic acid caused mesenteric vasoconstriction. After endothelial denudation, the dilator response to anandamide was slightly reduced and was no longer inhibited by SR141716A. In preparations from LPS-pretreated rats, SR141716A alone caused a significant and prolonged increase in perfusion pressure, whereas it had no such effect in control preparations perfused in vitro with or without LPS or after endothelial denudation in preparations from rats pretreated with LPS. We conclude that anandamide-induced mesenteric vasodilation is mediated by an endothelially located SR141716A-sensitive "anandamide receptor" distinct from CB1 cannabinoid receptors and that activation of such receptors by an endocannabinoid, possibly anandamide, contributes to LPS-induced mesenteric vasodilation in vivo.
Hypertension 1999 Jan
PMID:Mesenteric vasodilation mediated by endothelial anandamide receptors. 993 Nov 42

Carvedilol is a vasodilating beta-blocker and antioxidant approved for treatment of mild to moderate hypertension, angina, and congestive heart failure. SB 211475 (4-[2-hydroxyl-3-[[2-(2-methoxyphenoxy)ethyl]amino]propoxyl]-9H-++ +carbazol-3-ol), a hydroxylated carvedilol analogue, is an even more potent antioxidant in several assay systems. Carvedilol also has neuroprotective capacity with modulatory actions at N-methyl-D-aspartate (NMDA) receptors and Na+ channels. In the present study, we demonstrated that in cultured rat cerebellar neurons, SB 211475 has 28-fold greater antioxidant activity than carvedilol, but is 2- to 6-fold less potent, respectively, at inhibiting neurotoxic activities at Na+ channels and at NMDA receptor channels. To determine a biophysical rationale for these differential activities, small angle x-ray scattering data were obtained from model lipid and brain membrane bilayers containing either carvedilol, SB 211475, or dihydropyridine calcium channel blockers. Electron density profiles revealed that the location of SB 211475 was restricted to the glycerol backbone/hydrocarbon interface and significantly reduced membrane width by 5%, whereas the time-averaged location for carvedilol and flunarizine also extended to the hydrated surface of the bilayer. Comparison of carvedilol with several dihydropyridines showed a correlation between high ClogP values (lipophilicity), Na+ channel inhibitory potency, and bilayer localization. The antioxidant activity of SB 211475 could be explained by restricted intercalation into the glycerol phosphate/hydrocarbon interface, creating an increase in volume associated with the phospholipid acyl chains, which would then become resistant to lipid peroxidation. Differential channel modulation may also be explained by these membrane structural results, which indicate that carvedilol and the less spatially restricted dihydropyridine molecules are more likely to inhibit transmembrane receptor channels.
 ...
PMID:Neuroprotective activities of carvedilol and a hydroxylated derivative: role of membrane biophysical interactions. 997 86

Water plays many vital roles which must be maintained despite constant threat of water stress from the environment. Mechanisms to maintain these roles over the long-term involve intermediates of many metabolic pathways, such as glycerol, sucrose, free amino acids and their derivatives. In addition to viewing metabolic products as intermediates along energy-related pathways, nutrition researchers and epidemiologists should consider them as determinants of intracellular fluid maintenance. Satiety processes, oxidative-fuel selection, hormonal control, and intracellular-signaling processes can all be interpreted in terms of water-oriented metabolism. Water intake and hydration status can vary considerably, and may be inadequate for a sizeable proportion of Western adults. Due to the metabolic adaptations required to compensate for perpetually inadequate water, chronic sub-optimal water intakes may be highly relevant to chronic disease etiology. Preliminary evidence links water-oriented metabolism to obesity, diabetes, cardiovascular disease, hypertension and cancer. Development of a water-oriented perspective may reveal an important new area of research in human nutrition and epidemiology.
 ...
PMID:Another look at: fuel + O2 --> CO2 + H2O. Developing a water-oriented perspective. 1046 63

A fructose-enriched diet promotes hypertension in rats. We thought that an enhancement of the glycolytic and/or lipid disorder (s) that raise blood pressure could be the cause. Therefore, we studied 4 groups of Sprague-Dawley rats (+/-200 g): (1) control rats received a standard diet and tap water; (2) the glycerol group of rats received a standard diet and 0.54 mol/L glycerol in tap water; (3) the fructose group was given a fructose-enhanced diet (chow had 55% fructose instead of dextrin) and tap water; and (4) the fructose-glycerol group was given the fructose-enhanced diet and 0. 54 mol/L glycerol in drinking water. At the end of the second week, the findings were as follows. Blood pressure was 149+/-2 mm Hg in the fructose-glycerol group versus 129+/-2 (P<0.001), 131+/-2 (P<0. 001), and 140+/-3 (P<0.005) mm Hg in the control, glycerol, and fructose groups, respectively. Insulinemia was higher in the fructose-glycerol group than the control (P<0.001), glycerol (P<0. 001), and fructose groups (P<0.001); triglyceridemia was higher in the fructose-glycerol (P<0.02), fructose (P<0.05), and glycerol groups (P<0.02) than the control group. Thoracic aorta rings showed a lower ED(50) to 12,13-phorbol dibutyrate in the fructose-glycerol group than in the control (P<0.001), glycerol (P<0.002), and fructose groups (P<0.001). In conclusion, glycerol-fructose administration resulted in hypertriglyceridemia, hyperinsulinemia, and increased vascular sensitivity to 12,13-phorbol dibutyrate (with respect to the control group), and significantly greater expression of protein kinase C alpha and betaII (with respect to the glycerol group).
Hypertension 1999 Oct
PMID:Potential role of glycerol leading to rat fructose hypertension. 1052 99


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