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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain edema, leading to intracranial hypertension and brain herniation, is a major cause of death in fulminant liver failure. Astrocyte swelling is a prominent neuropathological feature in experimental fulminant liver failure. It has been postulated that the osmotic effects of glutamine, generated in astrocytes from ammonia and glutamate in a reaction catalyzed by glutamine synthetase, could mediate brain swelling. Normal rats and rats that received a portacaval anastomosis were infused with ammonium acetate or a sodium acetate control; brain water in cerebral cortex was measured with the gravimetry method, intracranial pressure by means of a cisterna magna catheter and cortical amino acids using high-performance liquid chromatography. Although brain edema was detected in both groups receiving ammonia, it was of a greater magnitude in portacaval anastomosis rats (80.94% + 0.17% vs. 80.24% + 0.09%, p < 0.01), resulting in the development of intracranial hypertension. When portacaval anastomosis rats were infused with ammonium acetate and pretreated with 150 mg/kg methionine-sulfoximine, an inhibitor of glutamine synthetase activity, brain edema was ameliorated and intracranial pressure did not rise. A dose-dependent reduction in brain glutamine levels was seen with increasing doses of methionine-sulfoximine; however, brain edema did not decrease beyond the 150 mg/kg dose, suggesting that the increase in brain water was not solely a result of glutamine accumulation. We conclude that brain edema of a magnitude that results in intracranial hypertension is more likely to develop in rats after portacaval anastomosis receiving a continuous ammonia infusion. The osmotic effects of glutamine appear to mediate, but only in part, the increase in brain water seen in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. 818 74

Recent reports indicate that alpha 1-Na,K-ATPase from Dahl salt-sensitive (DS) rats contains a glutamine for leucine substitution associated with increased Na-K coupling at unchanged maximal velocity. Genetic analyses suggest that alpha 1-Na,K-ATPase is a potential hypertension gene. Therefore, we investigated whether renal Na+ metabolism could constitute a pathophysiological link between the molecular/functional change in Na,K-ATPase and hypertension. We simulated the consequences of increased Na-K coupling on overall Na-bicarbonate reabsorption in a proximal tubular transport model that incorporates apical Na-H exchanger and basolateral Na-bicarbonate cotransporter, K+ channel, and Na,K-ATPase. As expected, increases in the levels of the former three transport pathways yielded higher Na+ reabsorption. In contrast, increases in the maximal velocity of the Na,K-ATPase with a normal 3:2 (Na-K) coupling ratio did not increase Na+ reabsorption when apical Na-H exchange activity was limiting overall absorption. However, an increase in the Na-K coupling from 3:2 to 3:1, reported for the mutant alpha 1-Na,K-ATPase in DS rats, was associated with greater Na+ reabsorption. This increase is a consequence of lower cytosolic pH and secondary stimulation of the Na-H exchanger at its allosteric H+ site. Decreased pH results from activation of Na-bicarbonate cotransport by Na,K-ATPase-dependent membrane hyperpolarization due to greater charge movement in 3:1 Na-K coupling. Thus, an increase in the Na-K coupling ratio results in an altered set point for cellular Na+ metabolism, with higher sodium reabsorption at unchanged Na,K-ATPase levels. The simulations thereby lend support for a unifying explanation for the salt sensitivity of DS rats, which has been proposed to stem from a mutation in the alpha 1-Na,K-ATPase.
Hypertension 1996 Feb
PMID:Pathophysiological consequences of changes in the coupling ratio of Na,K-ATPase for renal sodium reabsorption and its implications for hypertension. 856 44

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes pulmonary arterial hypertension and right ventricular hypertrophy due to hepatic metabolism to the alkylating pyrrole dehydromonocrotaline. Taurine a sulfonic amino acid, is hepato- and cardioprotective in a variety of conditions. We have examined the effects of taurine and its amidino analog, guanidinoethane sulfonate (GES), in rats injected i.p. with MONO (65 mg/kg). Taurine and GES were given as 1% solutions in drinking water beginning 14 days before administration of MONO and continuing for 14 days therafter, when the rats were killed. The MONO group had right ventricular hypertrophy and pulmonary hyperplasia. Compared with control, no significant changes in the right ventricle/left ventricle weight ratio, or the right ventricle/body weight ratio occurred in rats also given taurine of GES. Lung weights in these two groups were higher than in the control group, but below that of the MONO-alone group. The lethality of MONO over 14 days was decreased by taurine (LD50 for MONO alone 80 mg/kg; for MONO + taurine 121 mg/kg). Rats given only MONO had lower hepatic concentrations of GSH and cysteine (Cys), and higher activities of microsomal GSH transferase activity were no different from control. Gamma-Glutamylcysteine (Glu-Cys) synthetase and gamma-glutamyl transpeptidase activities were elevated. In MONO-injected rats given GES, hepatic GSH levels were higher and Cys levels were lower than in either the MONO alone or MONO + taurine groups. Gamma-Glu-Cys synthetase activity was depressed. Microsomal GSH transferase, GSH peroxidase and gamma-glutamyl transpeptidase activities were elevated. Livers of MONO-injected animals showed higher levels of serine (reversed by both taurine and GES) and glycine (Gly; reversed by GES) and lower levels of glutamine. Compared with control rats, the following changes occurred in serum amino acids: MONO alone: increased aspartate, taurine and lysine; taurine-supplemented: increased taurine, methionine (Met) and lysine, and decreased Gly; GES-supplemented: decreased asparagine, serine, Gly, arginine, taurine, and valine. Compared with the MONO-alone group, the taurine-supplemented group had higher glutamate (Glu), Met and alanine, and the GES-supplemented group higher alanine and lower serine, Gly, arginine and valine. We conclude that taurine protects against MONO-induced lethality and right ventricular hypertrophy. GES also protects against right ventricular hypertrophy. However, these agents act by different mechanisms, taurine preventing many of the biochemical changes induced by MONO, with GES inducing additional changes.
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PMID:Effects of taurine and guanidinoethane sulfonate on toxicity of the pyrrolizidine alkaloid monocrotaline. 857 99

A patient with a history of cerebrovascular disease, hypertension, and previous gastrectomy developed metabolic alkalosis and myoclonus. His medications included the anti-hypertensive agents nicardipine hydrochloride, delapril, prazosin; dihydroergotoxin and ticlopidine for cerebral infarction; estazolam for insomnia; azuren-L-glutamine compound and S-M powder. In addition, he had taken 12 grams per day of Ohta's Isan antacid, which contained 625 mg sodium bicarbonate per 1.3 g of antacid powder over a 6-month period. This antacid is commonly used in Japan. This is the first report of a case of metabolic alkalosis and myoclonus secondary to ingestion of a commercially available antacid in Japan.
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PMID:Metabolic alkalosis and myoclonus from antacid ingestion. 883 8

Taste preferences are altered to reflect physiological needs and to support the recovery from nutritional disorders. The central mechanism both recognition for and adaptation to a deficient essential nutrient, i.e. L-lysine, have been unveiled that the feeding center in the hypothalamus is a primary center nucleus to induce a neuronal plasticity responding to dietary intake of deficient nutrient in the brain and peripherally, such as sense of taste and its concentration change. Changing preferences may act as an alarm, signaling protein malnutrition or metabolic adult disease, such as hypertension for saltiness, diabetes for sweetness, etc. In addition, our consumption of alcohol beverage is still increasing despite of one of candidate to induce the hepatic disorders, because pharmacological function of alcohol in the brain is welcome for people enjoying meal or being relieved from stresses. Preference for both L-alanine and L-glutamine was observed when alcoholic rats fell in the hepatic disorder. Acute alcohol loading induced suppression of motor activity and the hepatic dysfunction, but both amino acids did obviously protect these alcoholic symptoms. People should have to require a little bit more specific L-amino acid physiologically and pharmacologically depending upon different states among aging, lifestyle, metabolic diseases and various stresses.
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PMID:[A new pharmacological and physiological aspects of L-amino acids]. 950 1

Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.
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PMID:Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes. 1007 66

Brain edema sufficient to cause intracranial hypertension and brain herniation remains a major cause of mortality in acute liver failure (ALF). Studies in experimental animal models of ALF suggest a role for ammonia in the pathogenesis of both encephalopathy and brain edema in this condition. As part of a series of studies to evaluate the therapeutic efficacy of ammonia-lowering agents, groups of rats with ALF caused by hepatic devascularization were treated with L-ornithine-L-aspartate (OA), an agent shown previously to be effective in reducing blood ammonia concentrations in both experimental and human chronic liver failure. Treatment of rats in ALF with infusions of OA (0.33 g/kg/h, intravenously) resulted in normalization of plasma ammonia concentrations and in a significant delay in onset of severe encephalopathy. More importantly, brain water content was significantly reduced in OA-treated rats with ALF. These protective effects of OA were accompanied by increased plasma concentrations of several amino acids including glutamate, gamma-aminobutyric acid (GABA), taurine, and alanine, as well as the branched-chain amino acids, leucine, isoleucine, and valine. Increased availability of glutamate following OA treatment provides the substrate for the major ammonia-removal mechanism (glutamine synthetase). Plasma (but not cerebrospinal fluid) glutamine concentrations were increased 2-fold (P <.02) in OA-treated rats, consistent with increased muscle glutamine synthesis. Direct measurement of glutamine synthetase activities revealed a 2-fold increase following OA treatment. These findings demonstrate a significant ammonia-lowering effect of OA together with a protective effect on the development of encephalopathy and brain edema in this model of ALF.
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PMID:L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. 1046 68

Recent studies in Caucasian populations have shown an association of the Leiden mutation in factor V with preeclampsia (PE). It consists of a substitution of a G (G1691) with an A (A1691) at nucleotide position 1691 in exon 10, resulting in arginine instead of glutamine at residue 506 at the factor V cleavage site for activated protein C (APC); it contributes to the resistance to APC. The purpose of this study was to determine whether the Leiden mutation is associated with pregnancy-induced hypertension (PIH), including PE, in Japanese women. We examined the genotypes of factor V of 71 Japanese patients with PIH and 109 controls. None of the 180 Japanese women carried the factor V Leiden mutation. To date, the factor V Leiden mutation is rare and not a common cause of PIH in Japan. The results may suggest that there is a significant ethnic difference in the role of the Leiden mutation in compounding the risk factors in the pathogenesis of PIH between Japanese and Caucasian populations.
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PMID:The factor V Leiden mutation is not a common cause of pregnancy-induced hypertension in Japan. 1062 7

We have proposed a combined osmolar-hemodynamic disturbance to explain the presence of brain edema in fulminant hepatic failure, a major cause of death in this disorder. The concept of an osmotic disturbance in the brain, emphasizing the presence of astrocyte swelling and low-grade cerebral edema, has been expanded to the entire spectrum of liver disease. The mechanism of cerebral hyperemia in patients with FHF and brain swelling has been studied in experimental models linking hyperammonemia and glutamine generation in astrocytes to the development of this hemodynamic alteration. Measures to control cerebral hyperemia, such as mild hypothermia, are effective in preventing the development of brain edema in experimental models as well as intracranial hypertension in human disease.
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PMID:Pathophysiology of brain edema in fulminant hepatic failure, revisited. 1172 92

Human alpha-chymase is an efficient angiotensin (AT) converting enzyme, selectively hydrolyzing AT I at Phe8 to generate bioactive AT II, which can promote cardiac hypertrophy, vascular stenosis, and hypertension. Some related enzymes, such as rat beta-chymase 1, are much less selective, destroying AT by cleaving at Tyr4. Comparisons of chymase structure and activity led to speculation that interaction between AT and the side chain of Lys40 or Arg143 accounts for the human enzyme's marked preference for Phe8 over Tyr4. To test these hypotheses, we compared AT hydrolysis by wild-type chymase with that by mutants changing Lys40 or Arg143 to neutral residues. Lys40 was exchanged for alanine, the residue found in canine alpha- and rat beta-chymase 1, the latter being dramatically less selective for hydrolysis at Phe8. Arg143 was exchanged for glutamine found in rat beta-chymase 1. The Lys40Ala mutant is a dog-like enzyme retaining strong preference for Phe8 but with Tyr4 hydrolytic rates enhanced 16-fold compared to wild-type human enzyme. Thus, of 40 residues mismatched between dog and human enzymes, a single residue accounts for most of the difference in specificity between them. The Arg143Gln mutant, contrary to prediction, remains highly Phe8-selective. Therefore, Lys40, but not Arg143, contributes to human chymase's remarkable preference for AT II generation over destruction.
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PMID:Lys40 but not Arg143 influences selectivity of angiotensin conversion by human alpha-chymase. 1200 14


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