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)

We have previously demonstrated that a 12 kD hypertension-associated protein (HAP) is elevated in essential hypertension and that this protein has the characteristics of natriuresis, inhibition of Na-K-ATPase, displaces 3H-ouabain from binding sites, and is vasoconstrictive in vitro. In the present study, plasma from 101 patients were examined [25 normals (N)<age 50, 13 N >age 50, 7 with acute congestive heart failure (CHF), 24 with chronic renal failure (CRF), on dialysis, 5 with idiopathic hyperaldosteronism (PA) and 27 with essential hypertension, untreated (EHT)]. Plasma was extracted with 32% acetonitrile, then analyzed by DELFIA for marinobufagenin and ouabain. In addition, from 32 patients (6 N <50, 6 N >50, 5 CHF, 5 CRF, 6 EHT, and 4 PA) SDS gradient gels were obtained. The 12 kD bands were extracted, analyzed for Na-K-ATPase inhibition, marinobufagenin and ouabain, and compared to 14 kD and 21 kD bands. Marinobufagenin was found to be elevated in CRF, EHT, PA and CHF. Ouabain was increased only in PA. When the relative optical densities of the 12 kD and 21 kD bands were contrasted, CRF, PA, and EHT were found to be increased and CHF to be decreased in the 12 kD band, with no discernible changes in the 21 kD bands. Following extraction of the bands, Na-K-ATPase inhibitory activity measured 38% in 18 pooled 12 kD bands, with essentially no activity found in the 14 kD or 21 kD bands. Thus only the 12 kD HAP band possessed all of the attributes of natriuretic hormone.
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PMID:Simultaneous measurement of marinobufagenin, ouabain, and hypertension-associated protein in various disease states. 968 18

Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344 x NB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,K-ATPase in aortic sarcolemma were studied. The ACTH treatment for 8 days resulted in increased systolic blood pressure (151 +/- 12.4 v 121 +/- 4.0 mm Hg, P < .01), inhibition of Na,K-ATPase in aortic sarcolemma (2.99 +/- 0.35 v 5.43 +/- 0.17 micromol ADP/mg(prot)/h), and increases in plasma concentration of marinobufagenin-like (0.44 +/- 0.06 v 0.21 +/- 0.05 nmol/L), but not ouabain-like (0.09 +/- 0.01 v 0.10 +/- 0.04 nmol/L) immunoreactivity. In dissociation enhanced lanthanide fluoroimmunoassay (DELFIA), serial dilutions of plasma from ACTH-treated rats extracted with 25% and 80% acetonitrile, respectively, demonstrated parallelism to the calibration curves of ouabain and marinobufagenin. These findings suggest that an endogenous bufodienolide Na,K-ATPase inhibitor, rather than an endogenous ouabain-like compound, is increased after 8 days of treatment of rats with ACTH.
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PMID:Plasma marinobufagenin-like and ouabain-like immunoreactivity in adrenocorticotropin-treated rats. 968 40

We report an isocratic, HPLC procedure for assay of the orally administered hypertension drugs [atenolol, amlodipine, nifedipine, nitrendipine, nimodipine and felodipine given in retention order] of which atenolol, an aryloxypropanolamine beta-blocker is administered with anyone of the other five dihydropyridine calcium channel blockers in combined hypertension therapy. The drugs were dissolved in methanol and 20 microliters of a mix of the drugs was injected onto a reverse phase JASCO-metaphase ODS (250 x 4.0 mm) 5 mu column. Any one of the six drugs could be used as the internal standard. The drugs were resolved by elution with a pH 4.5 equivolume mobile phase of acetonitrile-0.01 M KH2PO4, with pH adjustments done with H3PO4 (flow-rate 1.5 ml min-1). The column effluent was monitored at 250 nm. The detector response (peak height ratio) was linear in the dynamic range of 25-3200 ng ml-1 of these drugs, with the detection limits at approximately 15 ng ml-1. Full statistical evaluation of the data including linear regression (least-square fit) analysis was performed. The suggested procedure has the advantage that all the five dihydropyridine derivatives can be quantified alone or in formulation with atenolol.
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PMID:Isocratic, simultaneous reversed-phase high-performance liquid chromatographic estimation of six drugs for combined hypertension therapy. 991 13

Cod liver oil (CLO) is known to contain a complex mixture of triacylglycerols (TAGs) in which the component fatty acids include: myristic (C(14:0), M), C(14:1) (M(1)), palmitic (C(16:0), P), palmitoleic (C(16:1), P(1)), stearic (C(18:0), S), oleic (C(18:1), O), linoleic (C(18:2), L), arachidic (C(20:0), A), C(20:1) (A(1)), eicosapentaenoic (EPA, C(20:5), A(5)), docosanoic (C(22:0), D), docosaenoic (C(22:1), D(1)), and docosahexaenoic (DHA, C(22:6), D(6)). Because of the presence of EPA and DHA in cod liver oil, it has been used for several generations as a nutritional supplement, and recommended for the relief of various physiological ailments including arthritis, depression, and high blood pressure. Consequently, it was of interest to develop a sample preparation protocol that would enable rapid screening of such a chemically complex and nutritionally useful oil. Thus, we have analyzed two commercial brands of cod liver oil by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). There was no significant difference between the mass spectral profile of the two CLO brands. alpha-Cyano-4-hydroxycinnamic acid, dissolved in acetonitrile/tetrahydrofuran, was used as the matrix. MALDI-TOFMS produced only sodiated triacylyglycerol molecules [M + Na](+). Based on the sodiated TAGs, 64 TAG assignments were made, and these include MM(1)L, MML, MMO and MMS, M(1)P(1)L MP(1)L, P(1)P(1)P, PPP, P(1)P(1)Ln, P(1)PLn, PPL, PPO, P(1)LnLn, PLnLN, PLLn, PLL, POL, POO, P(1)A(6)Ln, P(1)A(5)Ln, P(1)A(5)L, PA(5)L PA(5)O, PP(1)D(6), OOL, OOO, SOO, SSS, P(1)LnD(6), PLnD(6), PLD(6), POD(6) (or P(1)A(5)A(1)), PA(5)A(1), OLA, OLA(1), SLA(1), SOA(1), SSA, LA(5)A(5) (or P(1)A(5)D(6)), OA(5)A(5) (or PA(5)D(6)), SA(5)A(5), LnA(1)A(5), OOD(6), SOD(6), SSD(6), LA(1)D(6), OA(1)D(6), OA(5)D(6), SA(5)D(6), SA(5)D(5), D(6)A(1)O, D(6)A(1)S, D(1)A(1)O, DA(1)O, D(1)D(6)O, and DD(6)O. The sample preparation method developed in this study could be used for the routine screening of oils that contain similar types of polyunsaturated TAGs.
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PMID:Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of cod liver oil and the effect of analyte/matrix concentration on signal intensities. 1045 46

Recent studies have provided evidence that hypoxia may stimulate the release of endogenous digitalislike factors (EDLF). Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep and may be associated with sympathetic activation and a high risk of developing hypertension. This study was designed to measure EDLF in the plasma of patients with OSA diagnosed by polysomnography, with patients being classified by the number of apneic-hypopneic episodes/h sleep (apnea-hypopnea index, AHI). Plasma was obtained in the morning from 8 male normotensive OSA patients (OSA-N) (AHI 70+/-6), 2 untreated hypertensive OSA patients (OSA-HT), and 11 age-matched healthy male controls (C). EDLFs of different hydrophobicities were separated from the same plasma sample by solid-state C18-cartridges with 25% acetonitrile (ACN) (EDLF-1) followed by 40% ACN (EDLF-2). This procedure recovered ouabain in the first fraction and digoxin and digoxigenin in the second. EDLF was quantified in pM ouabain-equivalents by a human placenta radioreceptor assay. EDLF-1 levels were similar for OSA-N and C (231+/-55 vs. 258+/-58), whereas EDLF-2 levels were increased in OSA-N (244+/-51 vs. 110+/-25 in C, p=0.02). Norepinephrine was increased in apneics. The two OSA-HT had EDLF and norepinephrine levels similar to OSA-N. These preliminary results suggest that OSA is associated with an increase in the more hydrophobic EDLF levels in both normotensive and hypertensive states. No significant increase was found for the less hydrophobic ouabain-like EDLF.
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PMID:Endogenous digitalislike factors in obstructive sleep apnea. 1101 25

A novel fast HPLC method was developed for the determination of cyclosporine A (CyA) and its two metabolites M17 (AM1) and M21 (AM4N) in blood. Whole blood was precipitated with zinc sulphate, extracted with diethyl ether, evaporated, dissolved in aqueous methanol and partitioned twice with n-hexane. Chromatography was carried out using a microbore RP-column under isocratic elution with acetonitrile-methanol-water (200:80:140, v/v/v) at 70 degrees C and a detector set at 205 nm. Linearity for all three compounds was tested in the range of 1-1000 ng/ml. Recovery was 97-109%, and a coefficient of variation was 1.6-8.8% depending on the particular compound and its concentration. The method was used for a group of renal transplant patients having an inadequate response to CyA therapy in order to evaluate the possible role of CyA and its metabolites on the occurrence of hypertension and other toxicological events.
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PMID:High-performance liquid chromatographic method for therapeutic drug monitoring of cyclosporine A and its two metabolites in renal transplant patients. 1112 82

Captopril, a well-known angiotensin converting enzyme (ACE) inhibitor, is widely used for treatment of arterial hypertension. Recent studies suggest that it may also act as a scavenger of free radicals because of its thiol group. Therefore, the present study describes a rapid, sensitive and relatively simple method for the detection of captopril in biological tissues with reverse-phase HPLC. Captopril was first derivatized with ThioGlo 3 [3H-Naphto[2,1-b]pyran,9-acetoxy-2-(4-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)phenyl-3-oxo-)]. It was then detected by fluorescence-HPLC using an Astec C(18) column as the stationary phase and a water:acetonitrile:acetic acid:phosphoric acid mixture (50:50; 1 mL/L acids) as the mobile phase (excitation wavelength, 365 nm; emission wavelength, 445 nm). The calibration curve for captopril was linear over a range of 10-2500 nM and the coefficient of variation acquired for the within- and between-run precision for captopril was 0.5 and 3.8%, respectively. The detection limit of captopril with this method was found to be 200 fmol/20 microL injection volume. Its relative recovery from biological samples was determined to the range from 93.3 to 105.3%. Based on these results, we believe that our method is advantageous for captopril determination.
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PMID:Determination of captopril in biological samples by high-performance liquid chromatography with ThioGlo 3 derivatization. 1174 37

Microspheres containing the anti-hypertension drug, felodipine, were prepared by the emulsion solvent evaporation method (o/o) using acrylate methacrylate copolymers, Eudragit RL PO and Eudragit RS PO, as wall materials. In order to increase the encapsulation efficiency, a mixed solvent system comprising 1:1 proportions of acetonitrile and dichloromethane was used as a dispersed phase. The morphology of the microspheres was evaluated using a scanning electron microscope, which showed a spherical shape with smooth surface. The mean sphere diameter was between 9.5-13.2 microm and the microencapsulation efficiencies ranged from 51.4-80.4%. The release profiles and encapsulation efficiencies depended strongly on the structure of the polymers used as wall materials. The release rate of the Eudragit RS PO microspheres was much lower than that of Eudragit RL PO microspheres. Whereas Eudragit RL PO microspheres followed the Higuchi rule, Eudragit RS PO microspheres exhibited a triphasic release profile. It is concluded that drug release rate can be controlled by choice of polymer type.
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PMID:Preparation and characterization of drug-loaded polymethacrylate microspheres by an emulsion solvent evaporation method. 1256 29

A high-performance liquid chromatographic method with electrochemical detection was developed for the simultaneous determination of five 1,4-dihydropyridines: amlodipine, nitrendipine, felodipine, lacidipine and lercanidipine. These drugs are widely used in the treatment of hypertension, angina pectoris and the therapy of cerebrovascular spasms of various origins. The chromatographic separation was performed on a Supelcosil LC ABZ + Plus C18 column with a mobile phase consisting of acetonitrile-10 mM acetate buffer (72:28, v/v) at a flow rate of 1 ml/min. The temperature was set at 30 +/- 0.2 degrees C. The amperometric detector, equipped with a glassy carbon electrode was operated at +1100 mV versus Ag/AgCl in the direct current mode. Under these chromatographic conditions, the drugs eluted in less than 12 min. The method showed to be linear over the range 4.5-15 microg/ml with a within-day and day-to-day repeatabilities in terms of R.S.D. lower than 15%, an accuracy greater than 98% and detection limits varying from 90 ng/ml (amlodipine) to 1.55 microg/ml (nitrendipine). The method was successfully applied to commercially available pharmaceuticals with relative errors lower than 5%. The validity of the method was examined comparing the results obtained with those of HPLC with photometric detection.
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PMID:Simultaneous determination of five 1,4-dihydropyridines in pharmaceutical formulations by high-performance liquid chromatography-amperometric detection. 1505 93

Nifedipine, a dihydropyridine calcium channel antagonist, is widely used in the treatment of hypertension and other cardiovascular disorders. A selective, sensitive and accurate high-performance liquid chromatographic method has been developed, validated and applied for determination of nifedipine in human plasma samples. A series of studies were conducted in order to investigate the effects of mobile phase composition, buffer concentration, mobile phase pH and concentration of organic modifiers, and to develop a convenient and easy-to-use method for quantitative analysis of nifedipine. The method involves solid-phase extraction on C18 cartridges. The chromatographic separation was accomplished on a Lichrocart Lichrospher 60 RP selectB column with a mobile phase composed of 0.020 mol/L KH2PO4 (pH 4.8) and acetonitrile (42:58, v/v). UV detection was set at 240 nm. The calibration curve was linear in the concentration range of 5.0-200.0 ng/mL for nifedipine in plasma and the limit of quantification was 5.0 ng/mL.
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PMID:Development of an HPLC method for the determination of nifedipine in human plasma by solid-phase extraction. 1662 37


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