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 numbers of monocytes and macrophages in the walls of cerebral blood vessels were counted on perfusion-fixed frozen brain sections (16 microns) of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), normotensive Wistar-Kyoto (WKY) rats, and young (16-week-old) and old (2-year-old) normotensive Sprague-Dawley rats (SD-16w and SD-2y, respectively) using monoclonal antibodies against rat macrophages (ED2). The staining was visualized with fluorescein-labeled second antibodies. The ED2-specific staining in brain sections was restricted to macrophages in a perivascular location. The number of perivascular cells per square millimeter of high-power field was significantly greater in SHR-SP (8.6 +/- 2.1; n = 4) and SHR (6.7 +/- 0.9; n = 6) than in normotensive WKY (4.0 +/- 0.5; n = 6; p < 0.01). The number of perivascular macrophages was also greater in SD-2y (7.5 +/- 2.7; n = 9) than in SD-16w (2.9 +/- 1.8; n = 8; p < 0.01). No ED2 staining was found in the resident microglia or in the endothelial cells, which were identified by double staining with rhodamine-labeled anti-factor VIII-related antigen antibodies. The results suggest that the stroke risk factors hypertension and advanced age are associated with increased subendothelial accumulation of monocytes and macrophages. This accumulation could increase the tendency for the endothelium to convert from an anticoagulant to a procoagulant surface in response to mediators released from these subendothelial cells.
J Cereb Blood Flow Metab 1994 Mar
PMID:Quantitation of perivascular monocytes and macrophages around cerebral blood vessels of hypertensive and aged rats. 811 30

The present series of experiments was carried out to investigate CBF autoregulation during fixed levels of acute increased intracranial pressure (ICP). Three groups of six rats each, one with normal ICP (8 mmHg), one with moderately increased ICP (30 mmHg), and one with severely increased ICP (50 mmHg), were investigated. ICP was maintained by continuous infusion of lactated Ringer solution into the cisterna magna. Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure--ICP, was increased by intravenously infused norepinephrine and decreased by controlled bleeding. In all groups the corresponding autoregulation curve included a plateau where CBF was independent of changes in CPP, demonstrating intact autoregulation. However, a significant shift of the lower limit of autoregulation (LL) toward lower CPP levels during severe intracranial hypertension was observed (p < 0.006). In the controls the LL was found at CPP = 73 +/- 6 mmHg, in moderately increased ICP the LL was 59 +/- 4 mmHg, and in severely increased ICP the LL was 51 +/- 4 mmHg. These results indicate that an acute elevation of ICP activates a reserve capacity of cerebral resistance vessels that dilate further below the normal physiological LL to maintain CBF at low levels of CPP.
J Cereb Blood Flow Metab 1994 May
PMID:Cerebral blood flow autoregulation in acute intracranial hypertension. 779 36

We have investigated whether there is a duration threshold for the effects of phenylephrine-induced hypertension on CBF, brain energy metabolism, and cerebral parenchymal specific gravity (SG) following transient forebrain ischemia in gerbils. Sixty gerbils were randomly assigned to one of the four treatment groups: one control group and three groups subjected to an increase of 25 mm Hg in MABP induced by treatment, 30 min after reperfusion, with phenylephrine for 15 min, 30 min, or 60 min. The local CBF was measured continuously, and the SG was evaluated 120 min after reperfusion. Sequential changes in brain energy metabolism, as shown by the ratio of phosphocreatine to inorganic phosphate (Pi), the beta-ATP/Pi ratio, and intracellular pH, were also measured. The 15-min induced hypertension regimen was most suited to the recovery of brain energy metabolism, which was associated with an increase in local CBF and a decrease in cerebral edema. These results demonstrate that a suitable duration can be chosen to optimize the beneficial effects of phenylephrine-induced hypertension on ischemic brain injury following transient forebrain ischemia.
J Cereb Blood Flow Metab 1996 Nov
PMID:Duration threshold of induced hypertension on cerebral blood flow, energy metabolism, and edema after transient forebrain ischemia in gerbils. 889 95

Cerebral large arteries dilate actively around the lower limits of CBF autoregulation, mediated at least partly by nitric oxide, and maintain CBF during severe hypotension. We tested the hypothesis that this autoregulatory response of large arteries, as well as the response of arterioles, is altered in spontaneously hypertensive rats (SHR) and that the altered response reverts to normal during long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor. In anesthetized 6- to 7-month-old normotensive Wistar-Kyoto rats (WKY), 4- and 6- to 7-month-old SHR without antihypertensive treatment, and 6- to 7-month-old SHR treated with cilazapril for 10 weeks, local CBF to the brain stem was determined with laser-Doppler flowmetry and diameters of the basilar artery and its branches were measured through a cranial window during stepwise hemorrhagic hypotension. The lower limit of CBF autoregulation shifted upward in untreated SHR to 90 to 105 mm Hg from 30 to 45 mm Hg in WKY, and it reverted to 30 to 45 mm Hg in treated SHR. In response to severe hypotension, the basilar artery dilated by 21 +/- 6% (mean +/- SD) of the baseline internal diameter in WKY. The vasodilation was impaired in untreated SHR (10 +/- 8% in 4-mo-old SHR and 4 +/- 5% in 6- to 7-month-old SHR), and was restored to 22 +/- 10% by treatment with cilazapril (P < 0.005). Dilator responses of branch arterioles to hypotension showed similar attenuation and recovery as that of the basilar artery. The data indicate that chronic hypertension impairs the autoregulatory dilation of the basilar artery as well as branch arterioles and that antihypertensive treatment with cilazapril restores the diminished dilation toward normal.
J Cereb Blood Flow Metab 1998 Mar
PMID:Attenuation and recovery of brain stem autoregulation in spontaneously hypertensive rats. 949 47

Large infarcts develop in pinealectomized rats subjected to middle cerebral artery occlusion, which was attributed to loss of antioxidant action of melatonin. However, melatonin also has vascular actions, and pinealectomy may induce hypertension. The authors investigated (1) whether hemodynamic factors contribute to infarct development in pinealectomized rats, (2) whether melatonin administration can reverse the unfavorable effect of pinealectomy on infarct formation, and (3) whether melatonin can reduce the infarct volume in nonpinealectomized rats subjected to focal transient ischemia (2 hours middle cerebral artery occlusion, 22 hours reperfusion). Rats were pinealectomized 3 months before ischemia to eliminate any possible action of pinealectomy-induced hypertension on stroke. Blood pressure and regional CBF values during ischemia and reperfusion were not significantly different between pinealectomized and sham-operated rats, suggesting that pinealectomy-induced increase in infarct was not related to hemodynamic factors. The infarct volume resumed to the level of sham-operated rats on melatonin administration. Injection of melatonin (4 mg/kg) before both ischemia and reperfusion reduced infarct volume by 40% and significantly improved neurologic deficit scores in pinealectomized as well as sham-operated rats subjected to middle cerebral artery occlusion. These data suggest that physiologic melatonin release as well as exogenously given melatonin has a neuroprotective action in focal cerebral ischemia.
J Cereb Blood Flow Metab 1999 May
PMID:Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia. 1032 18

Genomic screening of hybrids from stroke-prone (SHR-SP) and stroke-resistant spontaneously hypertensive rats (SHR) identified a STR1 locus on the rat chromosome 1, which correlates with the susceptibility to cerebral stroke but not with hypertension. The authors examined whether this genetic abnormality is associated with hemodynamic or metabolic alterations in the brain that can be detected before the manifestation of brain infarction. Starting at 6 weeks of age, SHR-SP were fed with a salt-rich diet to accelerate arterial hypertension. At the age of 12 weeks, animals developed functional symptoms and were age-matched with symptom-negative SHR-SP to differentiate between presymptomatic and postsymptomatic changes. Brains were investigated by multiparametric imaging comprising quantitative double-tracer autoradiography of CBF and cerebral protein synthesis (CPS); bioluminescence imaging of regional ATP, glucose, and lactate content; and umbelliferone fluoroscopic imaging of tissue pH. None of the animals exhibited focal hemodynamic or biochemical abnormalities. In symptom-negative SHR-SP, global CBF was 1.1+/-0.3 mL x g(-1) x min(-1), cortical CPS was 10.1+/-3.1 nmol x g(-1) x min(-1), and cortical ATP, glucose, lactate, and pH levels were in the normal range. In SHR-SP with functional symptoms, ATP, glucose, and lactate levels also were normal, but tissue pH exhibited periventricular alkalosis, CBF was significantly reduced to 0.7+/-0.2 mL x g(-1) x min(-1) (P < 0.001), and cortical CPS was significantly reduced to 6.7+/-2.1 nmol x g(-1) x min(-1) (P < 0.001). The decline in brain perfusion of SHR-SP correlated significantly with both the severity of functional deficits and the decline of protein synthesis. Our observations demonstrate that SHR-SP had already developed functional symptoms before the manifestation of overt brain infarcts and that the symptoms are initiated by a decline in global CBF and cortical CPS. Genetic abnormalities in SHR-SP are associated with a diffuse vascular process that results in global decompensation of blood flow well before the onset of focal brain infarction.
J Cereb Blood Flow Metab 1999 Nov
PMID:Hemodynamics and metabolism in stroke-prone spontaneously hypertensive rats before manifestation of brain infarcts. 1056 70

Pneumococcal meningitis resulting from Streptococcus pneumoniae has a death rate of 28% in adults. In severe head injury and stroke, inflammatory changes and intracranial hypertension are improved by induced hypothermia, which also is neuroprotective. We hypothesized that moderate hypothermia ameliorates inflammatory changes in experimental pneumococcal meningitis. Wistar rats were cooled systemically, and meningitis was induced by pneumococcal cell wall components. The increase of regional cerebral blood flow in the meningitis animals was blocked by hypothermia at 6 hours. The reduction of intracranial pressure correlated with temperature. The influx of leukocytes into the cerebrospinal fluid and levels of tumor necrosis factor alpha in the cerebrospinal fluid were decreased. Cooling the animals 2 hours after meningitis induction to 30.5 degrees C was also protective. We conclude that hypothermia is a new adjuvant approach to reduce meningitis-induced changes, in particular intracranial pressure, in the early phase of the disease.
J Cereb Blood Flow Metab 2000 May
PMID:Induced hypothermia in experimental pneumococcal meningitis. 1082 34

Hemostasis factors may influence the pathophysiology of stroke. The role of brain hemostasis in ischemic hypertensive brain injury is not known. We studied ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular fibrin deposition and activity of different hemostasis factors in brain microcirculation. In spontaneously hypertensive rats subjected to transient middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats, infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C activation and tissue plasminogen activator activity were reduced in spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P < 0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P < 0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces antithrombotic mechanisms in brain microcirculation, which may enhance cerebrovascular fibrin deposition and microvascular obstructions during transient focal cerebral ischemia, which results in greater neuronal injury.
J Cereb Blood Flow Metab 2000 Jun
PMID:Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model. 1089 83

Inhibition of angiotensin II AT1 receptors protects against stroke, reducing the cerebral blood flow decrease in the periphery of the ischemic lesion. To clarify the mechanism, spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were pretreated with the AT1 receptor antagonist candesartan (0.3 mg. kg.(-1) d(-1)) for 28 days, a treatment identical to that which protected SHR from brain ischemia, and the authors studied middle cerebral artery (MCA) and common carotid morphology, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), and protein expression in cerebral microvessels, principal arteries of the Willis polygon, and common carotid artery. The MCA and common carotid artery of SHR exhibited inward eutrophic remodeling, with decreased lumen diameter and increased media thickness when compared with WKY rats. In addition, there was decreased eNOS and increased iNOS protein and mRNA in common carotid artery, circle of Willis, and brain microvessels of SHR when compared with WKY rats. Both remodeling and alterations in eNOS and iNOS expression in SHR were completely reversed by long-term AT1 receptor inhibition. The hemodynamic, morphologic, and biochemical alterations in hypertension associated with increased vulnerability to brain ischemia are fully reversed by AT1 receptor blockade, indicating that AT1 receptor activation is crucial for the maintenance of the pathologic alterations in cerebrovascular circulation during hypertension, and that their blockade may be of therapeutic advantage.
J Cereb Blood Flow Metab 2003 Mar
PMID:Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT1 receptor inhibition. 1262 12

Uncontrolled increase in intracranial pressure (ICP) continues to be one of the most significant causes of early death in patients with acute liver failure (ALF). In this study, we aimed to determine the effects of indomethacin on ICP and cerebral perfusion pressure in twelve patients with ALF and brain edema (9 females/3 males, median age 49,5 (range 21 to 64) yrs.). Also changes in cerebral perfusion determined by transcranial Doppler technique (Vmean) and jugular bulb oxygen saturation (SvjO2) were measured, as well as brain content of lactate and glutamate by microdialysis technique. Finally, we determined the cerebral blood flow autoregulation before and after indomethacin injection. We found that indomethacin reduced ICP from 30 (7 to 53) to 12 (4 to 33) mmHg (P < 0.05). The cerebral perfusion pressure increased from 48 (0 to 119) to 65 (42 to 129) mmHg (P < 0.05), while Vmean and SvjO2 on average remained unchanged at 68 (34 to 126) cm/s and 67 (28 to 82) %, respectively. The lactate and glutamate in the brain tissue were not altered (2.1 (1.8 to 7.8) mmol/l and 34 (2 to 268) micromol/l, respectively) after injection of indomethacin. Cerebral blood flow autoregulation was impaired in all patients before injection of indomethacin, but was not restored after administration of indomethacin. We conclude that a bolus injection of indomethacin reduces ICP and increases cerebral perfusion pressure without compromising cerebral perfusion or oxidative metabolism in patients with ALF. This finding indicates that indomethacin may be valuable as rescue treatment of uncontrolled intracranial hypertension in fulminant hepatic failure.
J Cereb Blood Flow Metab 2004 Jul
PMID:The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure. 1524 Nov 88


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