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

Intracerebral haemorrhage (ICH) is much less common than ischaemic stroke (15% versus 85% in most Western studies), but is associated with a significantly worse prognosis. ICH is much more common in Asian populations, probably reflecting higher rates of small vessel disease, hypertension and genetic factors. Overall, ICH mortality rates approach 50% and there has been little effective treatment to date, except for the overall benefit from stroke unit care. Surgery for supratentorial ICH was not shown to be beneficial in a large recent trial of over 1000 patients, although controversies remain. For example, it still has an important role in selected patients with cerebellar ICH. Medical therapies to reduce brain edema and intracranial pressure, including glycerol and mannitol, are not of proven value. It is accepted that corticosteroids should not be used in ICH and may worsen outcomes. The management of acute hypertension is controversial and guidelines are based on little direct evidence.
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PMID:Medical management of haemorrhagic stroke. 1654 43

Diuretic therapy is a drug therapy that increases urine volume, but not glomerular filtration rate (GFR). The diuretics act predominantly on tubular sites; the drugs that increase GRF are the aminophyllines, the positive inotropy or vasoactive substances that increase afferent arteriolar flux or intraglomerular pressure. We can divide the diuretics into six categories: 1) carbonic anhydrase inhibitors: acetazolamide, dichlorphenamide, methazolamide; 2) osmotic diuretics: glycerol, mannitol, urea; 3) loop diuretics: furosemide, bumetanide, ethacrynic acid, piretanide, torsemide; 4) thiazide and thiazide-like diuretics: chlorothiazide, trichlormethiazide, indapamide, chlorthalidone, metolazone; 5) potassium-sparers: a) kidney epithelial sodium channel inhibitors: amiloride and triamterene; b) aldosterone receptor antagonists: spironolactone, canrenoate potassium, eplerenone; 6) ADH antagonists: lithium salts, demeclocycline and ethanol. Diuretic therapy is useful in treating acute and chronic renal insufficiency, congestive heart failure, cirrhosis, overhydration and hypertension. Diuretic therapy increases urine volume, ion loss (except Na+, K+), and modifies diffusion (dilute urine) and convection mechanisms (reduced tubular absorption). Therefore, diuretics are very useful non-dangerous drugs.
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PMID:[Diuretic therapy in heart failure]. 1663 1

Microdialysis is the only technique available for cerebral metabolic monitoring in the clinical setting. By the mean of a probe inserted in the brain, it provides an extracellular space sampling. Values of various substrates including cerebral glucose, lactate, pyruvate, glycerol or glutamate can be obtained at the bedside at intervals between minutes and hours. Values are critically dependent on the flow of the perfusion liquid and reflect a highly localized cerebral metabolism. Cerebral microdialysis improves our understanding of acute neurological events such as intracranial hypertension or decrease in brain tissue oxygen pressure. Cerebral microdialysis can be used for detection of ischaemia, especially after malignant stroke or vasospasm complicating subarachnoid haemorrhage. In these cases, it may influence the therapeutic management. Moreover, it permits the assessment of metabolic changes after therapeutic interventions. Finally, some markers (like lactate/pyruvate ratio) are related to outcome, especially after traumatic brain injury.
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PMID:[Cerebral microdialysis as a clinical tool]. 1671 67

A substantial increase in NADH production, arising from accelerated glycolysis, occurs in cardiac hypertrophy and this raises the question of how the NADH is oxidised. We have addressed this problem by reconstructing appropriate mitochondrial shuttles in vitro, using mitochondria from the left ventricles of both normotensive and spontaneously hypertensive rats at 5 and 24 weeks of age as model systems for left ventricle hypertrophy and hypertrophy/hypertension respectively. We found that most NADH oxidation occurs via a novel malate/oxaloacetate shuttle, the activity of which increases with time and with the progression of hypertrophy and development of hypertension as judged by statistical ANOVA analysis. In contrast, alpha-glycerol-phosphate and the malate/aspartate shuttles were shown to make only a minor contribution to NADH oxidation in a manner essentially independent of age and progression of hypertrophy/hypertension. The rate of malate transport in exchange with oxaloacetate proved to limit the rate of NADH oxidation via this malate/oxaloacetate shuttle.
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PMID:Mitochondria from the left heart ventricles of both normotensive and spontaneously hypertensive rats oxidize externally added NADH mostly via a novel malate/oxaloacetate shuttle as reconstructed in vitro. 1678 70

The present study was performed to assess the prophylactic effect of 7-nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS), in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1 mL per kg body weight) or 7-NI (5-20mg/mL per kg body weight) intraperitoneally. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 21-25 min. Pretreatment with intraperitoneal doses of 7-NI significantly improved survival during heatstroke (55-164 min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, neuronal damage score and nNOS expression in the hypothalamus, and tumor necrosis factor-alpha (TNF-alpha) in the serum. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of 7-NI before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, nNOS-dependent NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and neuronal damage score in the hypothalamus, as well as overproduction of TNF-alpha in the serum that occurred during heatstroke. The data show that reduction of nNOS-dependent NO(2)(-) with 7-NI causes attenuation of cerebrovascular dysfunction, hyperthermia, and TNF-alpha overproduction during heatstroke in the rat.
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PMID:Inhibition of neuronal nitric oxide synthase causes attenuation of cerebrovascular dysfunction in experimental heatstroke. 1695 Apr 11

The present study was performed to assess the prophylactic effect of baicalin, a flavonoid compound, in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1mL per kg body weight) or baicalin (10-40mg per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 20-28min. Pretreatment with intravenous doses of baicalin significantly improved survival during heatstroke (65-248min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, and dihydroxybenzoic acid (DHBA) in hypothalamus. In addition, both serum and hypothalamic levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as plasma levels of creatinine, serum urea nitrogen, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were elevated after heatstroke onset. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of baicalin before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, and the increased levels of NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and DHBA in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in both the serum and hypothalamus, and renal and hepatic dysfunction were suppressed by baicalin pretreatment. In contrast, both the serum and hypothalamic levels of IL-10 were significantly elevated by baicalin during heatstroke. We successfully demonstrated that baicalin can be used as a prophylactic agent for heatstroke. In particular, baicalin may protect against cerebrovascular dysfunction and brain inflammation in heatstroke.
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PMID:The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke. 1720 94

Apparent mineralocorticoid excess (AME) is a severe form of hypertension that is caused by impaired activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which converts biologically active cortisol into inactive cortisone. Mutations in HSD11B2 result in cortisol-induced activation of mineralocorticoid receptors and cause hypertension with hypokalemia, metabolic alkalosis, and suppressed circulating renin and aldosterone concentrations. This study uncovered the first patient with AME who was described in the literature, identified the genetic defect in HSD11B2, and provided evidence for a novel mechanism of reduced 11beta-HSD2 activity. This study identified a cluster of amino acids (335 to 339) in the C-terminus of 11beta-HSD2 that are essential for protein stability. The cluster includes Tyr(338), which is mutated in the index patient, and Arg(335) and Arg(337), previously reported to be mutated in hypertensive patients. It was found that wild-type 11beta-HSD2 is a relatively stable enzyme with a half-life of 21 h, whereas that of Tyr(338)His and Arg(337)His was 3 and 4 h, respectively. Enzymatic activity of Tyr(338)His was partially retained at 26 degrees C or in the presence of the chemical chaperones glycerol and dexamethasone, indicating thermodynamic instability and misfolding. The results provide evidence that the degradation of both misfolded mutant Tyr(338)His and wild-type 11beta-HSD2 occurs through the proteasome pathway. Therefore, impaired 11beta-HSD2 protein stability rather than reduced gene expression or loss of catalytic activity seems to be responsible for the development of hypertension in some individuals with AME.
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PMID:Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess. 1731 22

Although systemic cooling had recently been reported as effective in improving the neurological outcome after traumatic brain injury, several problems are associated with whole-body cooling. The present study was conducted to test the effectiveness of brain cooling without interference with the core temperature in rats after fluid percussion traumatic brain injury (TBI). Brain dialysates ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and injury (e.g., glycerol) markers before and after TBI were measured in rats with mild brain cooling (33 degrees C) and in the sham control group. Brain cooling was accomplished by infusion of 5 mL cold saline via the external jugular vein under general anesthesia. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximum grip angle in an inclined plane was measured to determine motor performance, whereas the percentage of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. As compared with those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, lactate-to-pyruvate ratio, and glycerol in brain and intracranial pressure, but lower values of cerebral perfusion pressure. Brain cooling adopted immediately after TBI significantly attenuated the TBI-induced increased cerebral ischemia and injury markers, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by brain cooling. We successfully demonstrate that brain cooling causes attenuation of TBI in rats by reducing cerebral ischemia and injury resulting from intracranial hypertension and cerebral hypoperfusion. Because jugular venipuncture is an easy procedure frequently used in the emergency department, for preservation of brain function, jugular infusion of cold saline may be useful in resuscitation for trauma patients.
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PMID:Effect of brain cooling on brain ischemia and damage markers after fluid percussion brain injury in rats. 1752 7

Both nitric oxide and glutamate contribute to ischaemic brain injury. Agmatine inhibits all isoforms of nitric oxide synthase and blocks N-methyl-d-aspartate receptors. In this study, we gave agmatine intraperitoneally and assessed its effect on fluid percussion brain injury in rats. Anaesthetised rats, immediately after the onset of fluid percussion traumatic brain injury (TBI), were divided into two major groups and given the vehicle solution (1mL/kg) or agmatine (50mg/kg) intraperitoneally. Mean arterial pressure, intracranial pressure, cerebral perfusion pressure, and levels of glutamate, nitric oxide, lactate/pyruvate ratio, and glycerol in hippocampus were monitored continuously within 120min after TBI. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximal grip angle in an inclined plane was measured to determine motor performance whereas the percent of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. Compared to those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, nitric oxide, lactate-to-pyruvate ratio, and glycerol in hippocampus and intracranial pressure, but lower values of cerebral perfusion pressure. Agmatine administered immediately after TBI significantly attenuated the TBI-induced increased hippocampal levels of glutamate, nitric oxide, lactate-to-pyruvate ratio, and glycerol, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by agmatine therapy. The present data indicate that agmatine may attenuate TBI by reducing the excessive accumulation of both glutamate and nitric oxide in the brain.
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PMID:Resuscitation from experimental traumatic brain injury by agmatine therapy. 1762 91

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.
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PMID:L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke. 1769 25


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