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

Plasma fibronectin concentration was determined by immuno-nephelometer analysis in 316 pregnant women between 22 and 38 weeks. The plasma fibronectin concentration increases progressively during normal pregnancy. From 22 to 30 weeks, the 90th percentile is 350 mg/l, and from 30 to 38 weeks it is 400 mg/l. 29 patients had a fibronectin level greater than 400 mg/l. Of this group, 95% of the creatinine's clearance were significantly lowered. From 30 weeks of gestation, the correlation between an elevated level of fibronectin and the development of hypertension is 100%. Our results confirm that this glycoprotein may be an early indicator of preeclampsia.
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PMID:[Fibronectin: an early marker of pre-eclampsia]. 261 26

During the past 15 years there has been a striking increase in the understanding of the molecular basis of cellular response to catecholamines. In addition to the two principal subtypes of beta-adrenergic receptors (beta 1 and beta 2), there are at least two (alpha 1, alpha 2) and very likely additional subtypes of alpha-adrenergic receptors. The discovery of guanine nucleotide binding (G) proteins as transducers of receptor occupancy to activation of second messenger systems provides a common theme in cellular regulation by catecholamines. Application of techniques such as radioligand binding and photoaffinity labeling have facilitated the direct identification, quantitation, and ultimately purification of alpha 1, alpha 2, beta 1, and beta 2 receptors. Each is a plasma membrane glycoprotein with a subunit molecular weight (without the carbohydrate portion of the glycoprotein) of 40,000 to 55,000 kDa. The recent cloning and sequencing of cDNAs for alpha 2-, beta 1-, and beta 2-adrenergic receptors has revealed that although each has a unique molecular structure, they appear to share several common features, including extracellular amino terminus, seven plasma membrane spanning domains, and intracellular carboxy terminus. The application of molecular biological techniques together with antireceptor antibodies, which will allow studies of adrenergic receptors independent of binding or functional properties, should help in answering the many unresolved questions related to activation and regulation of adrenergic receptors. Foremost among these is whether diseases such as hypertension are characterized by alterations in one or more adrenergic receptor subtypes.
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PMID:Adrenergic receptors. Evolving concepts on structure and function. 264 1

The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life.
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PMID:Epoetin: human recombinant erythropoietin. 268 Feb 41

Advances in biomedical technology have contributed effectively to the resolution of basic and clinical problems in Nephrology. Most of our insights on glomerular diseases come from animal models. Antibodies against components of the extracellular matrix have been shown to induce glomerular changes in vivo and the non-collagenous NC1 domain of type IV collagen has been demonstrated to contain the Goodpasture antigen. New pathogenetic mechanisms of glomerular injury are suggested by studies on the interaction of antibodies with glomerular cell surface antigens. Gp330, a glycoprotein expressed at the surface of glomerular visceral epithelial cells, has been recognized to be the most relevant antigen of Heymann nephritis. Antibodies able to crosslink gp330 bind to the antigen at the base of foot processes and the resulting immune complexes are shed into the subepithelial space where they form electron dense deposits. The complement membrane attack complex (C5b-9) is likely to be directly responsible for epithelial cell injury and proteinuria in this model. Other cell surface antigens of the glomerular capillary wall, such as dipeptidyl dipeptidase IV, podocalyxin, podoendin, have been characterized. A novel model of glomerular injury comes from the demonstration that a non-complement fixing monoclonal antibody to a surface sialo-glycoprotein (SGP-115/107) binds to glomerular visceral epithelial cells and causes morphological changes which appear epitope-specific and complement and leukocyte-independent. The mechanisms responsible for the progression of renal disease to glomerular sclerosis have been extensively explored in the last years. Among the hemodynamic factors intraglomerular hypertension has been established to play an important part, at least in some models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Nephrology]. 269 52

Doxazosin is a new quinazoline derivative that, like prazosin, has selectivity for alpha 1-receptors. A three-way crossover, randomized, open study in 18 patients with essential hypertension was conducted to investigate the clinical pharmacokinetics of 2, 4, and 8 mg doxazosin at steady state. The pharmacokinetics of the initial 2 mg dose was also studied. Doxazosin showed linear pharmacokinetics. Increases in doses from 2 to 8 mg (steady state) produced proportional increases in doxazosin serum levels (maximum plasma drug concentration [Cmax] minimum plasma drug concentration [C min], and O-24-hour area under the curve [AUC(p-24)], whereas half-life (t1/2) (19.4, 18.7, and 19.7 hours, respectively), volume of distribution (3.4, 3.4, and 3.6 L/kg, respectively), clearance from serum (2.2, 2.2, and 2.1 ml/min/kg, respectively), and degree of protein binding (1.2%, 1.0%, and 1.0% unbound, respectively) were dose independent. Similar t1/2 and time to reach peak concentration (tmax) were obtained with 2 mg initial dose and 2 mg steady state. alpha 1-Acid glycoprotein levels were unchanged during doxazosin treatment. Doxazosin lowered supine and standing systolic and diastolic blood pressure. The blood pressure reduction was associated with an increase in heart rate. Peak hypotensive and tachycardic effects occurred 5.7 +/- 0.1 hours after administration, whereas Cmax was achieved at 2.4 +/- 0.7 hours (tmax). Greater decreases in systolic blood pressure and increases in heart rate were seen in standing than in supine position. The reduction in standing systolic and diastolic blood pressure with 8 mg was greater than with 2 mg (P less than 0.05); however, the increases in heart rate were not different. Dizziness, headaches, and dry mouth were the most frequent side effects. This study indicates that doxazosin shows linear pharmacokinetics between 2 and 8 mg and that because of its long t1/2, once-a-day administration should be adequate for the treatment of hypertension.
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PMID:Clinical pharmacology of doxazosin in patients with essential hypertension. 295 Oct 51

The plasma fibronectin concentration was abnormally elevated (greater than 400 micrograms/ml) in 16 of 17 normotensive gravid women who subsequently developed preeclampsia. Of this group, 13 had elevated levels detectable greater than or equal to 4 weeks before the onset of hypertension. Our results indicate that plasma fibronectin levels can be abnormally increased long before the onset of clinical symptoms and that abnormalities of this glycoprotein may be an early indication of this pathologic process.
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PMID:Predictive value of fibronectin levels in normotensive gravid women destined to become preeclamptic. 370 30

The steroidogenic properties of a glycoprotein fraction (urinary ASF), isolated from normal human urine, were studied in collagenase-dispersed rabbit adrenal capsular cells in 1) define the requirements for its steroidogenic activity, and 2) assess its site and mode of action. When incubated with adrenal cell suspension at 37 degrees C for 2 hours, urinary ASF induced dose-related increases in both aldosterone and corticosterone production. However, urinary ASF was less potent (ED50 = 10(-9) M) than either angiotensin II (ED50 = 8 x 10(-11) M) or ACTH (ED50 = 4 x 10(-11) M). Increases in cyclic AMP accompanized the steroidogenic response to ACTH but not to either urinary ASF or AII. Deprivation of potassium in incubation media or the addition of ouabain (1 mM) during incubation completely inhibited the steroidogenic response to either urinary ASF, ACTH, or AII. Like ACTH and AII, urinary ASF increased conversion of corticosterone to aldosterone. Specific competitive antagonist of AII (Sar1, Thr8, AII) and ACTH ([I1e9]ACTH1-24) did not prevent the ASF-induced increase in aldosterone production. These results suggest that urinary ASF is readily distinguishable from ACTH. Although it shares similar steroidogenic properties with AII, the inability of AII antagonist to block its effects suggests that it acts at a separate receptor site.
Hypertension
PMID:Steroidogenic characteristics of a new aldosterone-stimulating factor (ASF) isolated from normal human urine. 626 51

To determine the effect of the duration and severity of hypertension on arterial wall metabolism 28 enzyme activities and several macromolecular complexes were histochemically studied in normotensive (WK), moderately (SHR) and strongly hypertensive (SP-SHR) rats at various ages. The results indicate that the abnormalities of 5' nucleotidase, acid esterase, cholinesterase and Alk.P. appeared in prehypertensive 4 w.old SHR. The posthypertensive changes, fluctuating in relation to the duration of hypertension, concerned: the pentose pathway, Krebs cycle and glycolosis -linked dehydrogenases; lysosomal enzymes; glycogen-phosphorylase and MAO; glycosaminoglycan and glycoprotein content. The structural and metabolic response presented several local and regional differences. The metabolic changes were greater in the aorta than in the caudal and femoral arteries. The comparison between SHR and SP-SHR indicates that the blood pressure (BP) at 170 mm Hg seems well tolerated during a long period of time. Severe lesions such as degeneration and failure of lipolytic activity in aortic smooth muscle cells (SMC), notable and early (8 mo.) in SP-SHR with 240 mm Hg were less intense and appeared later (13 mo.) in SHR with 190 mm Hg. The level of hypertension, rather than its duration, appears as a determining factor of posthypertensive vascular damage.
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PMID:Enzyme-histochemical changes in arteries of genetically hypertensive rats (SHR, SP-SHR). 632 44

In contrast to healthy persons, microvillous antigens of the proximal tubule were excreted at an increased rate in patients with kidney diseases as could be shown using specific antisera against brush border (BB) fragments (tissue-proteinuria, histuria). These urinary membrane components were immunologically completely identical with those antigens prepared from isolated kidney cell membranes. A glycoprotein of 240 000 dalton, containing mannose and N-acetylglucosamine was identified as a major immunoreactive constituent of the brush border surface and found to be part of a multienzyme complex. BB-antigens were excreted in urine of patients with glomerulonephritis, hypertension, pyelonephritis, multiple myeloma, after operations, after kidney transplantation, under cytostatic treatment, and after administration of radiopaque agents. Histuria of BB-antigens was significantly higher in patients with multiple myeloma and Bence-Jones-proteinuria compared to those patients where no Bence-Jones L-chains in urine became apparent. Selective kidney angiography and intravenous urography caused a significantly higher output of BB-antigens as compared to the control period (2 p less than 0,005). In a volunteer model, on the basis of BB-histuria, a different nephrotoxic potency of cephalosporins and aminoglycosides arose. In addition, beside soluble BB-antigens, also high molecular weight membrane vesicles were discovered in urine of patients after cytostatic treatment (cis-platinum), after x-ray contrast media, and after kidney transplantation. Both, soluble as well as supramolecular membrane vesicles were isolated from urine applying immunospecific affinity chromatography (anti-BS-agarose beads). Labeled antisera directed against the vesicle material of urine revealed a specific immunofluorescence of cortical tubule only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunodiagnosis of kidney tubular cell injuries using specific anti-membrane antibodies]. 638 21

The levels of protein associated with pregnancy (placental specific beta 1 glycoprotein, SP1, and pregnancy associated -alpha 2- globulin, alpha 2-PAG), immune function (complement, C3c) and inflammation (ceruloplasmin, C), were studied at term in groups of patients with normal and complicated primigravid and multigravid pregnancy. The levels of SP1 and C3c were similar in all the groups studied. In patients matched for parity, the levels of alpha 2-PAG were significantly lower than normal in preeclamptic primigravidas and in multigravidas with a history of preeclampsia in their first pregnancy. Ceruloplasmin levels were significantly elevated in preeclampsia patients and in patients with essential hypertension. It is suggested that reduced plasma alpha 2-PAG may be of prognostic value and have a role in the aetiology of preeclampsia whereas increased ceruloplasmin levels may be no more than an acute phase reactant resulting from pathological changes due to hypertension.
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PMID:Pregnancy-associated plasma protein levels at term in normal pregnancy, preeclampsia and essential hypertension. 657 51


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