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)

Hydralazine is used as an antihypertensive vasodilator drug. A specific and sensitive method for extraction and analysis of hydralazine by high-performance liquid chromatography (HPLC) with electrochemical detection was developed. Hydralazine and 4-methylhydralazine (internal standard) in plasma were derivatized at room temperature with salicylaldehyde. The derivatives were extracted in basic medium with a mixture of heptane, methylene chloride and isopentyl alcohol. A very good separation of hydralazine and 4-methylhydralazine from matrix material was achieved on a Supelcosil LC-18-DB (5 microns) reversed-phase column kept at 28 degrees C with a mobile phase of 66% methanol in 0.055 M citric acid/0.02 M dibasic sodium phosphate (pH 2.5). The hydralazine level was measured electrochemically by a screen oxidation mode. This method offers significant advantages in sensitivity, specificity and accuracy. Sample analysis by HPLC required less than 8 min. Application of the method to monitor plasma levels of hydralazine from a patient receiving the drug for the treatment of severe pregnancy-induced hypertension is discussed.
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PMID:Determination of hydralazine in human plasma by high-performance liquid chromatography with electrochemical detection. 355 80

On intravenous injection into cats, lysophosphatidic acid elicited a biphasic change in arterial blood pressure: sharp hypotension followed immediately by hypertension. Respiration was greatly disturbed immediately after injection of lysophosphatidic acid, and remained stimulated for a long period, and the heart rate increased during the period of hypertension. Unsaturated lysophosphatidic acids were more potent in evoking hypertension than saturated ones. The hypotensive activity of 1-palmitoyl-2-0-acetyl-sn-glycero-3-phosphate was about half that of 1-palmitoyl-2-lyso-sn-glycero-3-phosphate (lysophosphatidic acid). Elongation of the acyl chain at the sn-2-position of the glycerol moiety resulted in progressive reduction in the hypotensive activity. Chemically modified analogs with a head group, such as phosphoryl-methanol, ethanol, propanol and choline, had little or no activity. However, sn-2-acetyl-analogs of lyso-phosphatidyl cholines had hypotensive activity. 1-0-Hexadecyl-2-lyso-sn-glycero-3-phosphate, an alkyl-lyso-phosphatidic acid, had much stronger hypotensive activity than the corresponding acyl-lysophosphatidic acid, like its sn-2-0-acetyl analog. These structure-activity relationships of lysophosphatidic acids indicate the existence of their specific binding sites on cardiovascular cells.
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PMID:Effects of lysophosphatidic acids and their structural analogs on arterial blood pressure of cats. 384 54

A study to measure the pressor substance, called active pressor principle (APP), which is generated in incubated human plasma was performed using anesthetized and ganglion blocked rats. It was found that APP has properties characteristic of protein. APP was not extractable with mixtures of chloroform: methanol. APP was present at 50 to 70% saturation with ammonium sulfate. By treating the plasma with Pronase, the pressor activity of the plasma was almost completely abolished. The molecular weight of APP as determined by gel filtration was about 68,000. By adding diisopropyl fluorophosphate before incubation of the plasma, the generation of vasopressor substance was prevented. Treatment of the rat with captopril was ineffective in inhibiting the pressor effect of incubated plasma. It was found that the plasma of normal pregnant women generated significantly higher amounts of APP than the plasma of nonpregnant women. The plasma obtained from patients with pregnancy-induced hypertension generated significantly lower amounts of APP than the plasma of normal pregnant women. These findings suggest that a vasoactive protein (APP) is generated during simple incubation of plasma, and a serine protease is involved in the formation of this substance. Concerning the relevance of these results to blood pressure regulation in pregnancy-induced hypertension, probably APP is involved in blood pressure regulation via a compensatory mechanism.
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PMID:[Some properties of a vasopressor substance generated in human plasma by incubation and its clinical significance in pregnancy-induced hypertension]. 397 49

Betaxolol, a beta selective adrenoceptor antagonist recently approved for the treatment of hypertension, was determined by monitoring in chemical ionization mode with ammonia the [MH]+ ions of the trimethylsilyl derivatives of the drug and of its internal standard [2H5)betaxolol). Its pharmacokinetic profile obtained following administration of a 20 mg oral dose was characterized by a half-life of 22 h and a bioavailability of 85%. The main acid metabolite formed by elimination of the isopropylamino group may also be determined as the methyl TMS derivative but methylation with BF3-methanol should be used with caution since it may induce the opening of the cyclopropyl group. The routine electron capture determination procedure was compared to this mass spectrometric method and an excellent correlation was found (r = 0.9974). Both procedures have the same sensitivity (1 ng ml-1). Finally it was observed that under electron impact mode betaxolol trimethylsilyl side chain rearranged to lose TMS-O-CH=CH2; this elimination was confirmed by deuterium labelling studies.
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PMID:Determination of betaxolol, a new beta-blocker, by gas chromatography mass spectrometry: application to pharmacokinetic studies. 614 35

Four cases of basal ganglia infarction demonstrated by radionuclide brain imaging are presented. Bilateral basal ganglia infarctions in two patients were probably related to methanol intoxication and meningoencephalitis, and unilateral basal ganglia infarctions in two other patients were presumably due to cerebral atherosclerosis and/or hypertension. Various causes and mechanisms of basal ganglia infarction as well as positive findings of radionuclide brain imaging are briefly reviewed.
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PMID:Basal ganglia infarction demonstrated by radionuclide brain imaging. 675 40

Considering the recent rediscovery of the use of alpha-blocking agents in the treatment of hypertension and heart failure, we have studied the haemodynamic effects of 10-methyl-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate (nicergoline, Sermion), a new alpha-blocking ergot derivative, on the closed-chest anesthetized dog. For comparative reasons, the effects of nitroglycerin and nitroprusside were studied on the same model. The doses were adjusted to give an identical decrease in blood pressure after 30 min infusion (nearly 30%). Nicergoline did not change the heart rate, decreased total and femoral arterial resistance, did not change the cardiac output or the femoral flow, as opposed to nitroglycerin which decreased the cardiac output and systolic volume, causing a reflex tachycardia and femoral constriction, confirming its predominantly venous effect. Nitroprusside did not cause tachycardia, and the femoral resistances were increased, though less so than with nitroglycerin. Both nitroglycerin and nitroprusside apparently had no direct effect on myocardial performance, whilst nicergoline seemed to increase the myocardial compliance (by a decrease of the sympathetic tone). This drug merits further attention in that it is readily soluble and can easily be administered i.v., for treatment of acute heart failure, for example.
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PMID:Some haemodynamic effects of nicergoline, a new alpha-blocking agent, in the closed-chest anaesthetized dog as compared with nitroprusside and nitroglycerin. 679 41

Esmolol is an ultra short-acting intravenous cardioselective beta-antagonist. It has an extremely short elimination half-life (mean: 9 minutes; range: 4 to 16 minutes) and a total body clearance [285 ml/min/kg (17.1 L/h/kg)] approaching 3 times cardiac output and 14 times hepatic blood flow. The alpha-distribution half-life is approximately 2 minutes. When esmolol is administered as a bolus followed by a continuous infusion, onset of activity occurs within 2 minutes, with 90% of steady-state beta-blockade occurring within 5 minutes. Full recovery from beta-blockade is observed 18 to 30 minutes after terminating the infusion. Esmolol blood concentrations are undetectable 20 to 30 minutes postinfusion. The elimination of esmolol is independent of renal or hepatic function as it is metabolised by red blood cell cytosol esterases to an acid metabolite and methanol. The acid metabolite, which is renally eliminated, has 1500-fold less activity than esmolol. Methanol concentrations remain within the range of normal endogenous levels. Clinically, esmolol is used for the following: (i) situations where a brief duration of adrenergic blockade is required, such as tracheal intubation and stressful surgical stimuli; and (ii) critically ill or unstable patients in whom the dosage of esmolol is easily titrated to response and adverse effects are rapidly managed by termination of the infusion. In adults, bolus doses of 100 to 200mg are effective in attenuating the adrenergic responses associated with tracheal intubation and surgical stimuli. For the control of supraventricular arrhythmias, acute postoperative hypertension and acute ischaemic heart disease, doses of < 300 micrograms/kg/min, administered by continuous intravenous infusion, are used. The principal adverse effect of esmolol is hypotension (incidence of 0 to 50%), which is frequently accompanied with diaphoresis. The incidence of hypotension appears to increase with doses exceeding 150 micrograms/kg/min and in patients with low baseline blood pressure. Hypotension infrequently requires any intervention other than decreasing the dose or discontinuing the infusion. Symptoms generally resolve within 30 minutes after discontinuing the drug. In surgical and critical care settings where clinical conditions are rapidly changing, the pharmacokinetic profile of esmolol allows the drug to provide rapid pharmacological control and minimises the potential for serious adverse effects.
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PMID:Esmolol. A review of its therapeutic efficacy and pharmacokinetic characteristics. 775 50

A reproducible and selective supercritical fluid chromatography (SFC) method was developed for the analysis of felodipine, a drug indicated for the treatment of hypertension. Methanol-modified carbon dioxide was employed as the SFC mobile phase with both electron capture detection (ECD) and multi-wavelength detection (MWD) being used simultaneously for analyte determination. Chromatography limit of detection (LOD) and limit of quantitation (LOQ), linear dynamic range (LDR) and injection precision were obtained in order to assess chromatographic and detector performance for both the SFC/MWD and SFC/ECD/MWD systems. The method was shown to be stability indicating since felodipine could be separated from its potential oxidative degradation product, H152/37, in under 6 min (felodipine k' = 2.44). Sample throughput was increased by 60% with the SFC assay vs LC. The optimized SFC method was shown to be equivalent to an existing LC/UV procedure for the analysis of a sustained-release tablet while realizing a 92% saving in disposable solvent waste. In order to achieve further solvent savings overall, supercritical fluid extraction (SFE) with 8% methanol-modified carbon dioxide as the extraction fluid was used to extract felodipine from a sustained-release tablet (as opposed to traditional solvent extraction). Comparable drug recoveries were obtained with SFE sample preparation technique when either SFC or LC extract analysis was utilized.
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PMID:Analysis of felodipine by packed column supercritical fluid chromatography with electron capture and ultraviolet absorbance detection. 781 74

Nifedipine, (1,4-dihydro-2,6,dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylic acid dimethyl ester) a calcium channel blocker widely used in treatment of hypertension, is strongly photolabile. This may represent a problem in patients taking nifedipine and in handling of nifedipine samples. Reactive radical intermediates were determined and characterized in the process of nifedipine illumination using EPR spectroscopy. On illumination of nifedipine by daylight or by a mercury lamp, a nitroxide radical, RIIL-NIFNO.X was observed (in the first step), in various solvents like benzene, cyclohexane, methanol, acetonitrile, dimethylsulphoxide, or aqueous suspensions of liposomes. RIIL-NIF represents the nifedipine skeleton centered with phenyl group, and X is an EPR silent substituent. The generation of RIIL-NIFNO.X is coupled with the formation of nitroso compound, RIIL-NIFNO, as characterized by UV-visible spectroscopy. In a further step, RIIL-NIFNO abstracts hydrogen from nifedipine skeleton under the formation of RIIL-NIFNO.H radical. In addition to this, in system containing RIIL-NIFNO and unsaturated lipids, nitroxide radicals RIIL-NIFNO.RLIPIDS are formed probably via a pseudo Diels-Alder mechanism (RLIPIDS represents lipidic skeleton). The unusually easy photochemical activation of nifedipine is probably stimulated by photosensitization of its nitro group interacting with suitably positioned hydrogen or carboxylic methyl ester group from the pyridinyl ring.
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PMID:Reactive radical intermediates formed from illuminated nifedipine. 786 71

Hypertension has been linked to opening of the blood-brain barrier and may be related to the expression of the smooth muscle alpha-actin gene in contractile cells at the brain microvasculature. However, the cellular origin (i.e., endothelial cells, pericytes, smooth muscle cells) of the alpha-actin mRNA in the brain microvasculature is not clearly identified. Therefore, we investigated the abundance of actin mRNA by Northern blot analysis in isolated brain microvessels and in brain microvascular endothelial or pericytes in tissue culture. All samples showed the characteristic 2.1 kb transcript corresponding to cytoplasmic beta and gamma isoform mRNA. The 1.7 kb transcript corresponding to smooth muscle alpha-actin was detected in freshly isolated bovine brain microvessels, in primary cultures of brain microvascular pericytes, or endothelial cells; the latter cultures contain both endothelial cells and pericytes. The alpha-actin mRNA was absent in a cloned bovine brain endothelial cell line. The relative abundance of the alpha/(beta + gamma) actin transcript ratio was: cultured pericytes > freshly isolated microvessels > endothelial primary. The cellular distribution of the smooth muscle alpha-actin immunoreactive protein was studied by immunocytochemistry in cytospun/methanol-fixed isolated bovine brain microvessels with a monoclonal antibody directed to the amino-terminal decapeptide of the smooth muscle alpha-actin isoform. This antibody reacted strongly with precapillary arterioles of isolated microvessels, whereas no immunostaining was observed in either capillary endothelial cells or in pericytes. In conclusion, the alpha-actin mRNA is expressed in brain microvascular pericytes in tissue culture, but the immunoreactive alpha-actin protein is not expressed in brain microvascular pericytes in vivo. These data suggest that either 1) alpha-actin gene expression is induced in capillary pericytes in tissue culture or 2) alpha-actin mRNA in brain capillary pericytes in vivo is subject to translational repression resulting in no detectable alpha-actin protein under normal conditions.
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PMID:Differential expression of alpha-actin mRNA and immunoreactive protein in brain microvascular pericytes and smooth muscle cells. 788 22


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