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

Estimation and measurement of serum osmolality can be of value in the clinical management of certain forms of critical illness. Osmolality is a measure of the concentration of osmotically active particles, or solutes, in a solution. Only low-formula weight ions and uncharged molecules that are present in relatively high concentrations contribute significantly to serum osmolality. Serum osmolality can be easily estimated from the three major osmotic constituents of normal serum (sodium, urea, and glucose) by a simple formula. An understanding of serum osmolality, its laboratory measurement, its bedside estimation, and the concept of the osmole gap, is crucial in making a preliminary diagnosis of methanol and ethylene glycol intoxication, as well as a few other related compounds. There are important caveats to this use of the osmole gap, because under certain circumstances both false-positive and false-negative interpretations may occur. The osmole gap may also be helpful for confirming pseudohyponatremia, as a gauge for dosing mannitol and glycerol when used to treat intracranial hypertension, and as a prognostic indicator in circulatory shock.
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PMID:The serum osmole gap. 798 82

The effects of recombinant human interleukin-2 covalently linked to polyethylene glycol (PEG-IL-2) or interleukin-2 (IL-2) on hypertension and in vitro suppressor T cell function in the spontaneously hypertensive rats (SHR) were investigated. Male young prehypertensive (4 weeks old) SHRs and adult (10 weeks old) SHRs with established hypertension were injected with low (5,000 units (u)/kg) or high (50,000-100,000 u/kg) dose of PEG-IL-2 or IL-2 as a single bolus or repeated injections. Systolic blood pressure was measured twice weekly using the tail-cuff technique. Systolic blood pressure in the PEG-IL-2 or IL-2 treated animals, irrespective of age, dose, or route of injection, did not differ significantly from that measured in vehicle-treated controls over a 10 week period. Mean arterial pressure measured by intra-arterial catheter was 159 +/- 7 mm Hg 10 weeks after treatment with repeated injections of 5,000 u/kg of PEG-IL-2 and 158 +/- 9 mm Hg in vehicle-treated controls. All rats injected with IL-2 had IL-2-specific IgG antibody in their sera. None of the PEG-IL-2 treated rats had any detectable anti-IL-2 antibodies in their sera. Thus, PEG-IL-2 showed far less immunogenicity than IL-2. Suppressor T (Ts) cells generated from adult SHR spleen cells failed to suppress pokeweed mitogen (PWM)-driven immunoglobulin G (IgG) synthesis. PEG-IL-2 or IL-2 supplementation both in vitro and in vivo restored the ability of adult SHR to generate Ts cells able to inhibit IgG synthesis. Our data suggest that PEG-IL-2 or IL-2 administration does correct a prominent defective Ts cell activity found in adult SHR, but that correction of this immune abnormality is not attended by an attenuation of hypertension.
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PMID:The effects of PEG-interleukin-2 and interleukin-2 on essential hypertension and cellular immune function in the spontaneously hypertensive rat. 846 27

Seven clerical workers were evaluated in 1993, 8 months after exposure to vaporized 2-butoxyethanol (2-BE; also called butyl cellosolve or ethylene glycol monobutyl ether [EGMBE or EGBE]), which had been applied overnight to strip the floor of their file room. At the time of exposure, they had noted intense eye and respiratory irritation, marked dyspnea, nausea, and faintness, suggesting a concentration of 2-BE in the air of 200-300 parts per million (ppm). All seven workers later experienced recurrent eye and respiratory irritation, dry cough, and headache. Four months after the exposure, cherry angiomas began to appear on the arms, trunk, and thighs of six workers, who voiced concerns about the possibility of cancer. Our evaluation found no evidence of hematologic, liver, lung, or renal toxicity, but elevations in the erythrocyte sedimentation rate and blood pressure of each subject were found. Workplace air sampling found no detectable 2-BE, but traces (0.1-0.2 ppm) of formaldehyde were identified. Irritant symptoms abated after the group was moved to a room with better ventilation, and the mild hypertension gradually cleared, but new cherry angiomas have continued to appear 5 years after the acute exposure, as the initial ones persisted. These angiomas occur in healthy persons as they age but in this instance appear to have resulted from a single overexposure to 2-BE. We felt confident in reassuring the workers that they would suffer no serious consequences from this exposure.
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PMID:Eruptive cherry angiomas and irritant symptoms after one acute exposure to the glycol ether solvent 2-butoxyethanol. 987 82

Although controversial, a number of reports have suggested that calcium antagonists can retard or prevent the progression of various renal diseases in experimental models. Nevertheless, there are few data related to tubulointerstitial changes in these studies. On the other hand, hyperoxaluria is a recognized cause of tubulointerstitial lesions, and this could contribute to the development of hypertension and chronic renal failure. The aim of the present study was to evaluate a possible beneficial effect of amlodipine, a 1,4-dihydropyridine class of calcium antagonist, in a model of primary tubulointerstitial lesion produced by hyperoxaluria. Two-month-old male Sprague-Dawley rats were separated into 4 groups for a 4-week period: G1 (control; tap water only); G2 (hyperoxaluric); G3 (hyperoxaluric plus amlodipine treatment); and G4 (amlodipine treatment). G2 and G3 rats were given 1% ethylene glycol (a precursor for oxalates) in drinking water, and G3 and G4 rats were given amlodipine 2 mg. kg(-1). d(-1) by gavage. At the end of the study, we evaluated by semiquantitative scores (0 to 4) the different renal tubulointerstitial lesions, urinary albumin excretion, renal function by creatinine clearance, and blood pressure. Rats belonging to the hyperoxaluric group treated with amlodipine (G3) had fewer tubulointerstitial lesions, as follows: (1) inflammatory infiltrate score: 3.31+/-0.07 versus 0.23+/-0.12; P<0.05; (2) tubular atrophy score: 3.33+/-0.33 versus 0.50+/-0.22, P<0.05; (3) interstitial fibrosis score: 2.76+/-0.34 versus 0.31+/-0. 16, P<0.05; (4) oxalate deposits score: 3.66+/-0.33 versus 0.09+/-0. 08, P<0.05; (5) lower urinary albumin excretion (11.3+/-2 versus 27+/-4.5 mg/d, P<0.01); and (6) higher creatinine clearance (1. 22+/-0.08 versus 1.13+/-0.08, P<0.01) compared with the hyperoxaluric group untreated with amlodipine (G2). On the other hand, there were no significant changes in blood pressure in any group. In view of these data, we suggest that amlodipine, probably by nonhemodynamic mechanisms of action, can provide an important benefit in the prevention of epithelial tubular cell injury and inflammatory response and therefore in the prevention of the progressive tubulointerstitial fibrosis caused by oxalates.
Hypertension 1999 Oct
PMID:Effects of amlodipine on tubulointerstitial lesions in normotensive hyperoxaluric rats. 1052 73

Maintenance of constant drug levels in the body for those drugs that are used in management of hypertension is extremely beneficial. This can be successfully achieved by delivering the antihypertensives as osmotically-controlled drug-delivery system that essentially eliminates the influence of pH on the drug release. The main objective of this study was to evaluate the main effects of the formulation variables on the release of captopril from osmotically-controlled drug-delivery system coated with a custom-made cellulose acetate (CA) pseudolatex reported earlier. A secondary objective was to identify a suitable antioxidant for incorporating in the formulation as the drug undergoes metal-catalyzed oxidative degradation. The drug showed good stability (> or = 90% intact captopril) in solution in the presence of ascorbic acid for a period of 48 h. A seven-factor, 12-run Plackett-Burman screening design was employed to study the main effects of amounts of Polyox(R) N10 and N80, Carbopol(R) 934P and 974P, sodium chloride, orifice size, and % coating weight gain. The response variable was cumulative percent of drug released in 12 h, Y(3), with constraints on lag time Y(1) and time for 50% drug released Y(2)amount of sodium chloride (1.97).
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PMID:Captopril gastrointestinal therapeutic system coated with cellulose acetate pseudolatex: evaluation of main effects of several formulation variables. 1060 77

Salt moderation is often recommended to prevent excessive increases in blood pressure during pregnancy, particularly in women who are prone to pregnancy-induced hypertension; however, the vascular effects of low dietary salt intake during pregnancy are unclear. We investigated whether a low-salt diet during pregnancy alters the mechanisms of vascular smooth muscle contraction. Active stress and (45)Ca(2+) influx were measured in endothelium-denuded aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either a normal-sodium (NS, 1% NaCl) or low-sodium diet (LS, 0.2% NaCl) for 7 days. The mean arterial pressure was as follows: virgin/NS 108 +/- 8, virgin/LS 117 +/- 7, pregnant/NS 102 +/- 3, pregnant/LS 117 +/- 4, RUPP/NS 119 +/- 3, and RUPP/LS 133 +/- 6 mm Hg. Phenylephrine (Phe) caused concentration-dependent increases in active stress and (45)Ca(2+) influx that were greater in RUPP rats than in normal pregnant or virgin rats and were enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. High KCl (16 to 96 mmol/L), which stimulates Ca(2+) entry from the extracellular space, also caused increases in active stress that were greater in RUPP than in normal pregnant, in pregnant/LS than in pregnant/NS, and in RUPP/LS than in RUPP/NS rats. The Phe-induced (45)Ca(2+) influx--active stress relation was greater in RUPP/NS than in pregnant/NS and was enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. In Ca(2+)-free (2 mmol/L ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetra-acetic acid) Krebs, stimulation of intracellular Ca(2+) release by Phe (10(-5) mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. Thus, a low-salt diet in pregnant and RUPP rats is associated with increases in vascular reactivity that involves Ca(2+) entry from the extracellular space but not Ca(2+) release from the intracellular stores. The enhancement of the Phe-induced Ca(2+) influx--active stress relation in pregnant and RUPP rats on a low-salt diet suggests activation of other vascular contraction mechanisms in addition to Ca(2+) entry. Although it is difficult to extrapolate the experimental data in rats to clinical data in women, the increased vascular reactivity and Ca(2+) entry and the possible enhancement of additional vascular contraction mechanisms with a low-salt diet suggest that reduction of dietary salt intake should be carefully monitored during pregnancy and pregnancy-induced hypertension.
Hypertension 2002 Feb
PMID:Low-salt diet enhances vascular reactivity and Ca(2+) entry in pregnant rats with normal and reduced uterine perfusion pressure. 1188 75

This study tested the hypothesis that depressor responses caused by tempol are not associated with reductions in vascular O2- levels in urethane-anesthetized deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We compared the effects of intravenous (IV) administration of tempol, apocynin, superoxide dismutase-polyethylene glycol (PEG-SOD), and SOD on mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). In DOCA-salt rats, tempol (30 to 300 micromol/kg) dose-dependently decreased RSNA, MAP, and HR. Tempol (300 micromol/kg) decreased MAP from 140+/-5 to 83+/-4 mm Hg (P<0.05). HR decreased from 435+/-15 to 390+/-12 bpm (P<0.05). RSNA was reduced by 54%+/-6% from baseline. However, in the same rats, tempol did not reduce dihydroethidium-induced fluorescent signals in the aorta and vena cava. Apocynin (200 micromol/kg) did not lower MAP (142+/-5 mm Hg versus 140+/-6 mm Hg) or HR (428+/-15 bpm versus 420+/-13 bpm) and apocynin did not potentiate depressor responses caused by tempol. PEG-SOD (10 000 U/kg, bolus or 5000 U/kg bolus followed by a 30-minutes infusion of 500 U/kg/min) or SOD (25 000 U/kg, bolus or 10 000 U/kg bolus followed by a 30-minutes infusion of 1000 U/kg per minute) did not alter MAP or HR. It is concluded that depressor responses and decreases in HR and RSNA caused by acute tempol treatment are caused by direct sympathetic nerve activity inhibition that is not accompanied by SOD-mimetic action in the aorta or vena cava.
Hypertension 2004 Feb
PMID:Tempol lowers blood pressure and sympathetic nerve activity but not vascular O2- in DOCA-salt rats. 1470 56

The hypertensive effect observed with most cell-free haemoglobins has been proposed to result from NO scavenging. However, a newly developed PEG [poly(ethylene glycol)]-conjugated haemoglobin, MalPEG-Hb [maleimide-activated PEG-conjugated haemoglobin], is non-hypertensive with unique physicochemical properties: high O2 affinity, low co-operativity and large molecular radius. It is therefore of interest to compare the ligand-binding properties of MalPEG-Hb with unmodified cell-free HbA (stroma-free human haemoglobin). NO association rates for deoxy and oxyMalPEG-Hb and HbA were found to be identical. These results confirm the lack of correlation between hypertension and NO for a similar modified haemoglobin with high molecular radius and low p50 (pO2 at which haemoglobin is half-saturated with O2) [Rohlfs, Bruner, Chiu, Gonzales, Gonzales, Magde, Magde, Vandegriff and Winslow (1998) J. Biol. Chem. 273, 12128-12134]. The R-state O2 association kinetic constants were also the same for the two haemoglobins. However, even though the p50 of MalPEG-Hb is approx. half of that of HbA, the biphasic O2 dissociation rates measured at relatively high pO2 (150 Torr) were 2-fold higher, giving rise to a 2-fold lower R-state equilibrium association constant for MalPEG-Hb compared with HbA. Thus the O2 affinity of MalPEG-Hb is higher only at pO2 values lower than the intersection point of the O2 equilibrium curves for MalPEG-Hb and HbA. In summary, the present studies found similar rates of NO binding to HbA and MalPEG-Hb, eliminating the possibility that the lack of vasoactivity of MalPEG-Hb is simply the result of reduced molecular reactivity with NO. Alternatively, the unique O2-binding characteristics with low p50 and co-operativity suggest that the 'R-state' conformation of MalPEG-Hb is in a more T-state configuration and restricted from conformational change.
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PMID:Kinetics of NO and O2 binding to a maleimide poly(ethylene glycol)-conjugated human haemoglobin. 1517 10

Recently, it was demonstrated that superoxide oxidizes dihydroethidium to a specific fluorescent product (oxyethidium) that differs from ethidium by the presence of an additional oxygen atom in its molecular structure. We have adapted this new HPLC-based assay to quantify this product as a tool to estimate intracellular superoxide in intact tissues. Ethidium and oxyethidium were separated using a C-18 column and quantified using fluorescence detection. Initial cell-free experiments with potassium superoxide and xanthine oxidase confirmed the formation of oxyethidium from dihydroethidium. The formation of oxyethidium was inhibited by superoxide dismutase but not catalase and did not occur upon the addition of H(2)O(2), peroxynitrite, or hypochlorous acid. In bovine aortic endothelial cells (BAEC) and murine aortas, the redox cycling drug menadione increased the formation of oxyethidium from dihydroethidium ninefold (0.4 nmol/mg in control vs. 3.6 nmol/mg with 20 microM menadione), and polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) significantly inhibited this effect. Treatment of BAEC with angiotensin II caused a twofold increase in oxyethidium formation, and this effect also was reduced by PEG-SOD (0.5 nmol/mg). In addition, in the aortas of mice with angiotensin II-induced hypertension and DOCA-salt hypertension, the formation of oxyethidium was increased in a manner corresponding to superoxide production estimated on the basis of cytochrome c reduction. Detection of oxyethidium using HPLC represents a new, convenient, quantitative method for the detection of superoxide in intact cells and tissues.
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PMID:Detection of intracellular superoxide formation in endothelial cells and intact tissues using dihydroethidium and an HPLC-based assay. 1530 39

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.
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PMID:Cerebral vascular effects of angiotensin II: new insights from genetic models. 1609 17


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