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

Acid-base status and renal acid excretion were studied in the Dahl/Rapp salt-sensitive (S) rat and its genetically salt-resistant counterpart (R). S rats developed hypertension while on a very high salt diet (8%) and while on a more physiological salt diet (1%) and remained normotensive while on a very low salt diet (0.08%). Under the high salt diet, intracellular pH measured in freshly isolated thymic lymphocytes using 2',7'-bis (carboxyethyl)-5 (6)-carboxyfluorescein acetomethyl ester, a pH-sensitive dye, was lower in S than in R rats both when measured in the presence of HCO3/CO2 (7.32 +/- 0.02 vs. 7.38 +/- 0.02, respectively, P < 0.05) and in its absence (7.18 +/- 0.04 vs. 7.27 +/- 0.02, respectively, P < 0.05). Under the high salt diet, net acid excretion was higher in S than R rats (1,777 +/- 111 vs. 1,017 +/- 73 muEq/24 h per 100 g body wt, respectively, P < 0.001), and this difference was due to higher rates of both titratable acid and ammonium excretion. Directionally similar differences in intracellular pH and net acid excretion between S and R rats were also observed in salt-restricted animals. In S and R rats placed on a normal salt intake (1%) and strictly pair-fed to control food intake as a determinant of dietary acid, net acid excretion was also higher in S than in R rats (562 +/- 27 vs. 329 +/- 21 muEq/24 h per 100 g, respectively, P < 0.01). No significant difference in either blood pH or bicarbonate levels were found between S and R rats on either the 0.08%, 1%, or 8% salt diets. We conclude that renal acid excretion is augmented in the salt-sensitive Dahl/Rapp rat. Enhanced renal acid excretion may be a marker of increased acid production by cells from subjects with salt-sensitive hypertension.
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PMID:Renal acid excretion and intracellular pH in salt-sensitive genetic hypertension. 848 83

Diltiazem (DTZ) is a calcium antagonist widely used in the treatment of angina and hypertension. It is extensively metabolized in humans via N-demethylation, O-demethylation, deacetylation, and oxidative deamination, yielding a host of metabolites, some of which have potent pharmacological properties. After our initial identification of O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) as major metabolites of DTZ and our subsequent of identification of their chemical synthesis, an improved high-performance liquid chromatography assay was developed to determine the plasma concentrations of DTZ and seven of its major basic metabolites, including the previously unquantitated Mx and MB. The system consisted of a C18 analytical column protected by a C18 cartridge guard column and a variable wavelength ultraviolet detector set at 237 nm. The mobile phase was a mixture of methanol, 0.04 M ammonium acetate, and acetonitrile (38:36:26) containing 0.08% triethylamine, with final pH of the mobile phase adjusted to 7.5. The system was operated at room temperature isocratically at a flow rate of 1.2 ml/min. Using verapamil as an internal standard, DTZ and the basic metabolites in plasma were determined in young healthy volunteers (n = 21) and in patients with ischemic heart disease (n = 19) at steady state after repeated oral doses of 60 mg DTZ four times daily. Preliminary results show that steady-state plasma concentrations of DTZ and its metabolites were higher in the older patients than in young healthy subjects (p < 0.05).
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PMID:Steady-state plasma concentrations of diltiazem and its metabolites in patients and healthy volunteers. 884 19

Hypertension has been associated with increased activity of the Na(+)-H+ exchanger. To study the role played by protein kinase C in this process, we used chelerythrine, a potent and specific inhibitor of the kinase. After an acid load by ammonium chloride preincubation, platelets isolated from spontaneously hypertensive rats showed a faster and larger increase in intracellular pH than platelets from Wistar-Kyoto rats. The initial rate of intracellular pH recovery was 2.46 +/- 0.26 pH units per minute in spontaneously hypertensive rats and 1.74 +/- 0.19 in Wistar-Kyoto rats. For protein kinase C inhibition, platelets were incubated for 30 minutes with 10 mumol/L chelerythrine. This treatment induced a significant reduction in the recovery rate only in spontaneously hypertensive rat platelets, indicating that a pathway involving protein kinase C participates in the prestimulation of the exchanger in cells from this rat strain. Addition of chelerythrine reduced the baseline intracellular pH of platelets. No significant difference was found between the decrease of steady-state intracellular pH induced by chelerythrine in either rat strain. These findings indicate that this model of hypertension is characterized by increased Na(+)-H+ activity mediated by protein kinase C stimulation.
Hypertension 1996 Dec
PMID:Chelerythrine inhibits Na(+)-H+ exchange in platelets from spontaneously hypertensive rats. 895 90

Sixty two samples of amniotic fluid, collected by ultrasound guided amniocentesis, were submitted to biochemical investigation including 31 samples from women with pregnancy complicated by hypertension (studied group) and 31 samples deriving from healthy pregnant women (control group with). Both investigated and control groups consisted of pregnant women with the same gestational age of 37 +/- 2 weeks (34-40 weeks). The following ions were measured: NH4+, K+, Na+, Cl-, Mg++, total Ca, Ca++ and inorganic phosphorus (Pi). The ionic composition of amniotic fluid deriving from women with pregnancy complicated by hypertension was normal. The regular concentration of NH4+ ions in amniotic fluids of a studied group may suggest kidneys of the fetuses in pregnancy complicated by hypertension were as mature as in the normal pregnancy within the same gestational age.
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PMID:[Evaluation of the intrauterine fetus in hypertension--biochemical assessment of amniotic fluid. IV. Ions]. 929 36

The purpose of the present investigation is to reveal the specifics of the nutrition, nutritional behavior (habits), the prevalence of obesity and of certain chronic diseases among workers. The subjects were 264 workers (203 males and 61 females) from the ammonium production department of a fertilizer plant, divided into two age groups: under and over 30 years of age. The data were collected by means of a food-frequency questionnaire about daily nutrition and the average quantity of food. The nutritional status was assessed on the basis of BMI. All workers underwent clinical examinations conducted by a range of different experts, including an internal diseases specialist, a neurologist, a cardiologist, an opthalmologist, an otorhino-laryngologist, and a dermatologist. Twenty hematological and biochemical indicators in blood and serum were measured. Assessment of the individual energy intake showed that hyperenergetic nutrition was typical of 67% of workers because of extra intake of fat, which was seen in 87.9% of all individuals examined. The daily fat intake of over 40E% was typical for almost half the females (45.9%). All age and gender groups displayed hyperprotein nutrition with pronounced cellulose (fiber) deficit and a high daily sodium intake. The frequency of overweight individuals (BMI = 25, 1-30 kg/m2) was 43.9%, whereas that of obese individuals (BMI = > 30 kg/m2) was 23.1%. A total of 67% of workers had excessive body mass. The hypertension prevalence rose significantly from 6.9% in Group I to 34.5% in Group II, and to 57.4% in Group III. Coronary heart disease was rare, but the seven cases registered were among the overweight workers. The radiculitis prevalence among workers with normal body mass was two-fold lower in comparison with both groups (overweight and obesity). We conclude that hyperenergetic and unbalanced nutrition is a factor that determines the prevalence of overweight and obesity. A significantly higher percent of overweight and obese workers suffered from hypertension, liver disease, diabetes, coronary heart disease, and eye-vessel diseases. A tendency toward rising radiculitis and musculoskeleton system disease prevalence was seen that parallels the increase in BMI.
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PMID:Nutrition, nutritional habits, obesity, and prevalence of chronic diseases in workers. 1037 17

Abnormalities in acid-base regulation have previously been reported both in hypertensive humans and animals and a link between abnormalities in renal sodium handling and acid excretion may be particularly important in black hypertensives. The objectives of this study were to compare indices of urinary acid excretion (urinary pH, ammonium and titratable acid excretion) between normotensives and hypertensive people of African origin. Measurements were carried out in 86 black individuals of African origin in a case-control design (19 normotensive; 67 hypertensive). Of these, 17 normotensive and 17 patients with essential hypertension were matched for age, sex and weight. Group comparisons were carried out by unpaired t-tests or two-way analysis of variance and group values are given as means +/- s.d. Urinary pH was significantly higher in the hypertensives both in the unmatched groups and in the matched groups. In the 17 matched pairs: urinary pH in the hypertensive individuals was 6.36 +/- 0.54 and 5.84 +/- 0. 53 in the normotensives, respectively; P = 0.007. Additionally, urinary titratable acidity was significantly lower in the hypertensives than in the normotensives (25.4 +/- 13.7 vs16.7 +/- 10. 7 mmol/24 h; P = 0.047) but there were no significant differences in urinary ammonium excretion. The mechanisms for the apparent reduction in acid excretion in the hypertensives is not clear but these results highlight the possibility that hypertension in blacks is associated with abnormalities of renal sodium and hydrogen exchange with compensatory increases in renal ammonium production.
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PMID:Urinary acid-base excretion in normotensives and hypertensives of african origin. 1091 51

For the majority of hypertensive cases, no gene or combination of genes and environmental factors clearly leading to hypertension has been identified. Studies to identify "hypertension" genes have focused on the assessment of markers and candidate genes in the nuclear genome. In this study, we have chosen to assess the mitochondrial genome as a site of mutations possibly contributing to susceptibility to hypertension in black Americans who have progressed to end-stage renal disease (H-ESRD). The mitochondrial genomes of 58 H-ESRD and 58 normotensive individuals were systematically analyzed by means of a high-resolution restriction analysis. After stratification by the presence or absence of an African continent-specific HpaI site gain at bp 3,592, differences in the frequencies of mitochondrial DNA (mtDNA) restriction variants in both groups were examined by chi-square analyses. A total of six variants was identified with significant differences in one or both cohorts. An A10398G DdeI mutation in the ND3 gene was significantly increased in the H-ESRD cohort (H-ESRD, P = 0.048; normotensives, P = 0.20), as was an HaeIII T6620C/G6260A double mutation in the CO1 gene (H-ESRD, P = 0.05; normotensives, P = 0.48). The remaining four variants were a G2758A mutation in the 16SrRNA gene (identified by RsaI), T10810C in the ND4 gene (identified by HinfI), a G7028A/T7055C double mutation in the CO1 gene (identified by AluI), and finally, a A10086G mutation in the ND3 gene (identified by TaqI; also causing an Asn-->Asp amino acid change). The RsaI and HinfI variants were in strong linkage disequilibrium with the HpaI site and not amenable to further analysis. After correction of all P values for multiple comparisons, the ND3 A10086G (Asn-->Asp) mutation shown by TaqI remained statistically significant (P = 0.0036) in the H-ESRD cohort, not in the normotensive cohort. To the best of our knowledge, this is the first report of an increased prevalence of mitochondrial gene variants in hypertensive individuals. In addition, we have identified single-nucleotide polymorphisms in flanking regions of these genes. Although replication and further assessment are necessary, the current results support our hypothesis that mtDNA may account for a portion of hypertensive cases in black Americans with ESRD.
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PMID:Mitochondrial DNA mutations in black Americans with hypertension-associated end-stage renal disease. 1153 85

Angiotensin-II-cleaving angiotensinase A (aminopeptidase A, E.C. 3.4.11.7, ATA) plays an important role in glomerular haemodynamics. the pathophysiology of essential arterial hypertension and the induction of vascular disorders. In order to study biochemical and immunological properties of ATA, two isoforms (I and II) of the glycoprotein were isolated for the first time from human kidney cortex. Kidney cortex homogenate, digested with bromelain, was fractionated by ammonium sulphate precipitation and subsequent hydrophobic interaction chromatography, using a fast protein liquid chromatographic (FPLC) system. By anion-exchange FPLC (Mono Q column), the isoforms of ATA were eluted in two distinct peaks and were further purified by size-exclusion FPLC and preparative polyacrylamide gel electrophoresis. Biochemical, immunological and immunohistological characterization disclosed differences in the intrarenal localization, glycosylation Michaelis constant and apparent molecular mass (native and sodium dodecyl sulphate gel electrophoresis) but similar properties in the double-immunodiffusion technique. Polyclonal rabbit antibodies, raised against ATA isoforms I and II, precipitated an analogous antigen in urine from patients with renal tubular damage.
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PMID:Angiotensinase A (aminopeptidase A): properties of chromatographically purified isoforms from human kidney. 1212 12

Arterial hyperammonemia and cerebral vasodilatation correlate with cerebral herniation in patients with fulminant hepatic failure (FHF). Tacrolimus is a calcineurin inhibitor that passes the blood-brain barrier and may increase cerebrovascular tone and restrict cerebral ammonia influx. In this study, we determined if tacrolimus prevents cerebral vasodilatation and high intracranial pressure (ICP) in the rat with portacaval anastomosis (PCA) challenged to high arterial ammonia (NH4+) concentration. Seven groups of mechanically ventilated rats, with 6-9 rats in each group, were investigated within 48 hours after construction of a PCA (4 groups) or after sham operation (3 groups). Three groups of the rats received infusion of NH4+ and 4 groups received saline for approximately 180 minutes. Two groups of the PCA rats receiving either NH4+ or saline had an i.v. injection of tacrolimus (0.4 mg/kg) or vehicle before start of NH4+ or saline infusion. Cerebral blood flow (CBF) was monitored by a laser Doppler probe in brain cortex. ICP was monitored by placement of a catheter in the cerebrospinal fluid. CBF and ICP increased in PCA rats receiving NH4+ infusion compared to PCA controls and to all groups of sham-operated animals (P <.05). In the group of PCA rats pre-treated with tacrolimus before receiving ammonia infusion, the increase in ICP was ameliorated compared to the ammonia infused group receiving vehicle (P <.03). Tacrolimus also prevented an increase in CBF in the PCA group receiving NH4+ (P <.05) compared to the control groups. In conclusion, Tacrolimus prevents cerebral vasodilatation and ameliorates intracranial hypertension in PCA rats receiving NH4+ infusion. These findings indicate that tacrolimus could be of clinical value in the prevention of cerebral hyperemia, high ICP, and serious brain damage in patients with FHF.
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PMID:Tacrolimus ameliorates cerebral vasodilatation and intracranial hypertension in the rat with portacaval anastomosis and hyperammonemia. 1523 79

The effects of sulfur sources on the desulfurization activity of Rhodococcus erythropolis KA2-5-1 were investigated by using an exponential fed-batch culture technique. The feed rate of a sulfur source was controlled independently of the feed rate of ethanol, which was used as a carbon and energy source. Among the sulfur sources examined were dibenzothiophene (DBT), ammonium sulfate, L-cysteine, L-methionine, and 2-amino-ethanesulfonic acid. When the fed-medium contained DBT as the sole sulfur source, KA2-5-1 cells showed a maximum desulfurization activity of approximately 130 mmol 2-HBP kg-cell(-1) h(-1). Similar levels of enzyme activity were also achieved with inexpensive ammonium sulfate by using the exponential fed-batch culture technique. In addition, higher levels of desulfurization activity were achieved by increasing the dosage of the DBT desulfurization (dsz) operon and dszD gene in R. erythropolis KA2-5-1. The recombinant strain showed a maximum desulfurization activity of approximately 250 mmol 2-HBP kg-cell(-1) h(-1) in the exponential fed-batch cultures.
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PMID:Effect of sulfur sources on specific desulfurization activity of Rhodococcus erythropolis KA2-5-1 in exponential fed-batch culture. 1623 86


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