Angiotensin II receptors are exclusively of the AT1 subtype in cultured human vascular smooth muscle cells.
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1-Sarcosine-8-Isoleucine Angiotensin II↗
Biomedical subjects
M Schachter
Publications and source records attributed to M Schachter.
Different effects of platelet derived growth factor isoforms on DNA synthesis and migration in human vascular smooth muscle cells.
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Cell Movement↗
Comparison of effects of platelet-derived growth factor isoforms on signaling and DNA synthesis of human cultured saphenous vein cells.
We examined the effect of platelet-derived growth factor (PDGF)-AA, PDGF-AB, and PDGF-BB isoforms on DNA synthesis, Ca2+ mobilization, and tyrosine phosphorylation in cultured human saphenous vein cells cultured by an explant technique; confluent cells derived from passage 3 were used for all studies. DNA synthesis was measured by [methyl3H]thymidine uptake, intracellular [Ca2+] ([Ca2+]i) was measured with the Ca(2+)-sensitive indicator fura-2, and tyrosine phosphorylation was measured by Western blotting techniques. All three isoforms of PDGF stimulated [methyl3H]thymidine uptake concentration dependently, with similar potency. PDGF-AB induced significantly greater [methyl3H]-thymidine uptake than PDGF-BB, and PDGF-AA was much less effective than either PDGF-AB or PDGF-BB. The effects of all three isoforms were inhibited by tyrphostin-23, a selective inhibitor of tyrosine kinases PDGF-AB and PDGF-BB increased [Ca2+]i, although the maximum response to PDGF-AB was significantly less than that to PDGF-BB. Both isoforms increased [Ca2+]i by stimulating influx and intracellular release of Ca2+. PDGF-AA had no measurable effect on [Ca2+]i. All three isoforms increased tyrosine phosphorylation of a 170-kDa protein detected by Western blotting. Quantitative densitometry indicated that PDGF-BB induced greater tyrosine phosphorylation than PDGF-AB and both PDGF-BB and PDGF-AB induced markedly more tyrosine phosphorylation than PDGF-AA. PDGF isoforms have differing efficacies in terms of DNA synthesis, Ca2+ mobilization, and tyrosine phosphorylation by human saphenous vein cells.
Blotting, Western↗
Inhibition of human vascular smooth muscle cell proliferation by the novel multiple-action antihypertensive agent carvedilol.
We examined the antiproliferative effect of the novel multiple-action antihypertensive agent carvedilol on human vascular smooth muscle cells (VSMC). Carvedilol inhibited the increase in cell number induced by foetal calf serum (FCS) in 86% (18 of 21) of human VSMC grown both from saphenous vein (17.6 +/- 3.5% inhibition, mean +/- SEM, n = 15) and restenotic lesions (31.4 +/- 5.5% inhibition, mean +/- SEM, n = 5). Carvedilol had a greater antiproliferative effect than other beta-adrenoceptor antagonists. In comparison with calcium channel blockers, carvedilol (10 microM) elicited a degree of growth inhibition similar to that of verapamil, but was less effective than the dihydropyridine amlodipine at equimolar concentrations. Although carvedilol had a greater antiproliferative effect on cells derived from restenotic lesions cells than on control saphenous vein cells, the difference was not statistically significant. In the present study, the antiproliferative effect of carvedilol on human VSMC in vitro occurred at concentrations higher than those in plasma. Although this may represent a limitation to the clinical efficacy of carvedilol against proliferation of VSMC associated with hypertension and atherosclerosis, the apparent relative selectivity of carvedilol for restenosis-derived cells is a promising line of investigation.
Antihypertensive Agents↗
Clinical evidence of genomic imprinting in Tourette's syndrome.
Recent genetic studies of Tourette's syndrome (TS) have suggested a sex-specific expression of TS behaviors but not a sex-associated difference in their transmission. In a retrospective study designed to assess the influence of gender of the affected parent on childhood TS phenotype, we compared unmedicated TS subjects with patrilineal (n = 25) or matrilineal (n = 25) inheritance of TS, as determined by family history methodology, with respect to demographic variables, temporal profile of tic evolution, and clinical ratings of tics and associated behaviors, particularly obsessive-compulsive symptoms and attention deficit hyperactivity disorder (ADHD). Maternal transmission of TS was characterized by trends toward greater motor tic complexity and more frequent noninterfering rituals (p < 0.05); paternal transmission was associated with increased vocal tic frequency (p = 0.01), an earlier onset of vocal tics relative to motor tics (p < 0.01), and more prominent ADHD behaviors, including motor restlessness (p < 0.01). These findings are consistent with genomic imprinting in TS. Confirmation of this phenomenon promises not only to advance understanding concerning the genetic link between TS and ADHD but may also help to explain the apparent fit of competing models of genetic transmission in TS.
Adolescent↗
Role of polyamines in hypertension induced by angiotensin II.
OBJECTIVE: The aim was to investigate the involvement of polyamines in the development of cardiovascular hypertrophy in a rat angiotensin II infusion model of hypertension. METHODS: Rats were chronically infused with a low dose of angiotensin II (83 ng.min-1.rat-1) or vehicle by osmotic minipumps. The polyamine content of the cardiovascular organs and liver was measured by HPLC, and the blood pressure of conscious rats was determined by a tail cuff method. The mesenteric arterial beds were perfusion fixed in situ and medial and luminal cross sectional areas were determined by computer assisted planimetry. Cardiac hypertrophy was assessed by determination of ventricular:body weight ratios. RESULTS: Angiotensin II infusion caused an increased concentration of polyamines in the ventricles and aorta within hours of beginning the infusion, and within days in the mesenteric arteries. Polyamine content of the liver was unaffected. Hypertrophy of the myocardium and mesenteric arteries in association with the increased blood pressure was evident. CONCLUSIONS: A low dose of angiotensin II stimulates an early biochemical marker of growth, the polyamines, in cardiovascular tissues but not in the liver. The increase in tissue polyamines is associated with cardiovascular hypertrophy and the development of hypertension.
Angiotensin II↗
New ideas for treating hypertension.
Despite the wide range of anti-hypertensive drugs currently available many more are being developed, including entirely novel classes of compounds. This is not entirely surprising as a minority of patients do not respond to existing agents or are unable to tolerate them at therapeutic doses. It is also true that hypertension represents a very large international market. This brief review deals with the following classes of agents which are at various stages of development: (1) angiotensin receptor antagonists of the AT1 subtype, the first of which has recently been marketed in the UK; (2) renin inhibitors, whose development has been hindered by the poor bioavailability of all but the most recent compounds; (3) imidazoline (I1) receptor agonists, centrally acting drugs with relatively little sedating activity; (4) potassium channel openers, which act as potent vasodilators; (5) neutral endopeptidase inhibitors which potentiate the actions of atrial natriuretic peptides; and (6) endothelin antagonists, which are still in pre-clinical development. The potential clinical significance of these compounds is discussed.
Animals↗
Do KCa channels and carbonic anhydrase play a role in thiazide-induced hyperglycaemia?
Thiazide diuretics are widely used to treat hypertension, but their use is associated with impaired glucose tolerance. We propose that the diabetogenic action of thiazides may be due to their ability to open calcium-activated potassium (KCa) channels in pancreatic beta-cells.
Benzothiadiazines↗
Severe maternal and fetal electrolyte imbalance in pregnancy after gastric surgery for morbid obesity. A case report.
BACKGROUND: Gastric surgery for morbid obesity is considered a safe procedure with favorable effects on reproductive performance. Pregnancies after gastric restrictive operations are usually well tolerated by both mother and fetus. Some postoperative complications, however, do occur, although an association between such complications and adverse pregnancy outcomes has not been reported. CASE: A 40-year-old woman had a successful gastric operation for weight reduction but developed chronic, low grade gastro-intestinal obstruction as a late complication of surgery. Subsequent pregnancies ended in late abortion or premature delivery. During her last pregnancy, reported here in detail, severe and life-threatening fetomaternal electrolyte imbalances developed. CONCLUSION: Pregnancy following a gastric operation for morbid obesity may be complicated by severe metabolic disturbances that can jeopardize both the pregnant woman and her fetus. These pregnancy complications, which are related to the primary gastric surgery, are reported here for the first time.
Adult↗
Vasorelaxant actions of 5-OH-indapamide, a major metabolite of indapamide: comparison with indapamide, hydrochlorothiazide and cicletanine.
5-OH-Indapamide is a principal metabolite of indapamide, and possesses similar antihypertensive and diuretic properties. This study investigated the mechanisms of the acute vasodilator actions of 5-OH-indapamide, indapamide, hydrochlorothiazide and cicletanine and their interaction with ion channels in isolated guinea pig mesenteric arteries. Hydrochlorothiazide, cicletanine and 5-OH-indapamide relaxed noradrenaline-constricted vessels significantly more than K(+)-constricted vessels (P < 0.001) and the relaxations were reduced in the presence of charybdotoxin (P < 0.001). 5-OH-Indapamide-induced relaxation was reduced (by 42% at 30 microM) by glibenclamide (P < 0.001). Hydrochlorothiazide, cicletanine and 5-OH-indapamide (all at 10 microM) were weak Ca2+ antagonists shifting the Ca2+ dose-response curves half a log unit to the right (P < 0.01). Indapamide was a more potent inhibitor, a 10 microM concentration shifting the Ca2+ dose-response curve three log units to the right and reducing maximal-induced Ca2+ contraction by 72% (P < 0.001). Hydrochlorothiazide, cicletanine and 5-OH-indapamide-induced relaxations appear to be partly mediated via Ca(2+)-activated K+ channels; 5-OH-Indapamide-induced relaxation is also partly mediated via ATP-sensitive K+ channels. Indapamide is a potent Ca2+ antagonist.
Animals↗
Molecular Auger resonance Raman effect: A high resolution study on the resonance Auger decay of HBr after the Br 3d-->5p pi Rydberg transition.
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Journal Article↗
Evaluation of prenatally diagnosed hydronephrosis by morphometric measurements of the kidney.
A large number of hydronephrotic kidneys (108) were diagnosed prenatally in 69 infants between 1987 and 1991 and subsequently confirmed postnatally. Prenatal morphometric measurements were done in order to find reliable parameters for the detection of a group at risk for surgical treatment. A second aim of the study was to describe the natural history and management of hydronephrosis detected prenatally. We devised a classification of postnatal obstructive uropathy using ultrasonography and the renal scan. Accordingly, we classified the patients as having mild, moderate or severe hydronephrosis. A renal pelvic antero-posterior diameter (APD) of 9 mm or more, and a pelvic-to-renal APD ratio of 0.45 before 32 weeks of gestation and 0.52 thereafter, were found to be useful for the detection of severe outcome. Our new parameter, a pelvic-to-renal volume ratio of greater than 0.08, can also be used for this purpose.
Algorithms↗
External cephalic version after previous cesarean section--a clinical dilemma.
OBJECTIVES: To describe our limited experience with external cephalic version from breech to vertex presentation at term, with the use of ritodrine tocolysis, in women who had undergone a previous cesarean delivery. METHODS: Eleven parturients after previous cesarean delivery underwent external version after 36 gestational weeks, utilizing tocolysis with ritodrine, after excluding cases of low-lying placenta, severe oligohydramnion or ruptured membranes. Patients were then followed until delivery and scar examination was carried out after vaginal delivery, or at re-cesarean section, according to mode of delivery. RESULTS: All 11 attempted versions were successful. Six patients subsequently delivered vaginally and five by re-cesarean section. None of the uterine scars showed any signs of dehiscence. Three of the five infants delivered by re-cesarean section weighed over 4000 g, whereas all of the vaginally-delivered infants weighed under 3500 g. CONCLUSIONS: External cephalic version to vertex presentation after previous cesarean section was successful in all 11 carefully selected patients. No untoward effects were noted, and no signs of scar dehiscence were found. The safety and efficacy of this procedure after previous cesarean delivery should be examined further.
Adult↗
Development of proliferative retinopathy in a gestational diabetes patient following rapid metabolic control.
Rapid glucose control was achieved by insulin therapy in a patient diagnosed to have gestational diabetes at 8 weeks of pregnancy. A decrease of the initially high hemoglobin A1c level (16.2%) to normal values (5.9%) was achieved within 12 weeks. At 31 weeks severe bilateral proliferative diabetic retinopathy developed. To our knowledge this case is the first report of a patient with gestational diabetes who developed de novo proliferative diabetic retinopathy.
Adult↗
Multiple pathways for entry of calcium and other divalent cations in a vascular smooth muscle cell line (A7r5).
The influx of calcium in response to vasopressin receptor stimulation is an important component of excitation-contraction coupling. We have examined the routes by which Ca2+ and other divalent cations enter vascular smooth muscle cells using a cultured vascular smooth muscle cell line (A7r5). Confluent A7r5 cells were loaded with Fura-2 to permit measurement of intracellular divalent cation concentration (Ca2+, Ba2+, Mn2+). Combinations of excitation wavelengths (340/380, 340/356, 356/380 and 340/370) were used depending on the divalent cation being studied. Emission was measured at 510 nm for all studies. Ca2+, Ba2+ and Mn2+ permeated unstimulated A7r5 cells. Vasopressin increased intracellular Ca2+ in cells both in the presence and absence of extracellular Ca2+, although responses in the absence of extracellular Ca2+ were smaller and had no sustained component. Amlodipine, a voltage-dependent calcium channel blocker, had no effect on Ca2+ entry, but Ni2+ did block Ca2+ influx. Vasopressin-induced elevations of intracellular Ca2+ in Ca(2+)-free physiological saline were abolished by ionomycin and thapsigargin. In the presence of extracellular Ba2+ vasopressin increased intracellular Ca2+ transiently and caused a small sustained increase in intracellular Ba2+ concentration. Ionomycin and thapsigargin increased intracellular Ca2+ but had no effect on Ba2+ influx. In contrast vasopressin, ionomycin and thapsigargin had no effect on Mn2+ influx. Econazole and SKF 96365, imidazoles reported to be blockers of receptor-induced cation entry, increased intracellular Ca2+ by releasing intracellular Ca2+ from a different site to that mobilized by vasopressin or thapsigargin in A7r5 cells. Econazole and SKF 96365 partially inhibited passive influx of Ca2+ and Ba2+ but did not inhibit passive influx of Mn2+, or vasopressin-induced influx of Ba2+. U73122, a putative inhibitor of phospholipase C partially inhibited passive entry of Ca2+ but not passive entry of Mn2+ and Ba2+. U73122 also inhibited vasopressin-induced release of intracellular Ca2+ and agonist-induced Ca2+ influx but did not block vasopressin-induced Ba2+ influx. Divalent cations enter A7r5 cells by a number of routes - 'passive' pathway(s) that admit Ca2+, Ba2+ and Mn2+ and receptor-operated pathway(s) that are permeable to Ca2+, Ba2+ but not Mn2+. On the basis of ionic permeabilities and the effect of various blocking agents, there appear to be two distinct passive influx routes. One is permeable to Ca2+ and Ba2+ and is blocked by econazole or SKF 96365. The other is permeable to Mn2+ and is blocked by Ni2+. There also appear to be two different routes of divalent cation entry involved in responses to receptor activation.(ABSTRACT TRUNCATED AT 400 WORDS)
Barium↗
Consistent responses of the human vascular smooth muscle cell in culture: implications for restenosis.
PURPOSE: The mechanisms whereby restenoses occur at discrete sites within the vasculature remain uncertain. We have recently reported that vascular smooth muscle cells (VSMC) derived from patients with graft stenoses are resistant to growth inhibition by heparin. In this study, we have examined whether VSMC proliferation rates and responses to inhibition by heparin vary according to the individual or the anatomic site of origin. METHODS: Long saphenous veins from seven patients were divided into proximal, middle, and distal portions, and VSMC were cultured separately from each. VSMC proliferation in response to 15% fetal calf serum +/- 100 micrograms/ml heparin was measured by counting triplicate samples at 0, 3, 7, 10, and 14 days. This experiment was repeated from the second to the sixth passage (n = 6) and for artery and vein pairs derived from four additional patients. RESULTS: Differences between vein segment cultures of individual veins were found not to differ significantly from experimental error for either proliferation or heparin inhibition and were not altered by repeated passage (ANOVA). There were, however, significant differences in sensitivity to heparin inhibition between patients (p = 0.02) (ANOVA). There were no significant differences between paired samples of artery and vein for either proliferation or heparin inhibition (Mann-Whitney test). CONCLUSIONS: VSMC growth characteristics reflect the individual patient and are maintained in cell culture.
Analysis of Variance↗
Amenorrhea during the reproductive years--is it safe?
OBJECTIVE: To collate information relating specifically to amenorrhea of different etiologies in young women, the long- and short-term implications of these states, and the optimal therapeutic strategy to treat these conditions. DATA IDENTIFICATION: Studies related to these topics were identified through literature and Medline searches. STUDY SELECTION: Those studies that relate specifically to amenorrhea in women of reproductive age, including etiology, diagnosis, and the implications of replacement therapy or nontreatment of this state, were selected. RESULTS: Amenorrhea, as defined by the absence of menses for > or = 6 months, may be found in up to 3% of women in the reproductive years. Classification of amenorrhea involves defining the exact cause for the cessation of menses, be it hypothalamic, pituitary, ovarian, or lower genital tract in origin. The majority of amenorrheic young women have very low levels of estrogens, and a minority will have subnormal noncyclic estrogen levels, unopposed by P, due to anovulation. This distinction is important in considering the long-term implications of amenorrhea. Hypoestrogenic amenorrhea is associated with a significant loss of bone mineral density and the associated risk of osteoporosis and fractures. Lipoprotein profiles are also adversely affected, and this is associated with an increased risk of cardiovascular events. Anovulatory amenorrhea due to "unopposed" estrogen is associated with an increased risk of endometrial hyperplasia and endometrial carcinoma even in young patients. Therapy should be aimed at treating the underlying cause of amenorrhea, if possible, or reconstitution of an estrogen-P biphasic monthly cycle if not. CONCLUSIONS: Untreated amenorrhea is associated with significant long-term morbidity, especially in young women. Early recognition and institution of treatment will minimize late complications.
Aging↗
Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo-controlled study.
OBJECTIVE: To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS. SETTING: Specialized assisted reproduction unit. PATIENTS: Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration. INTERVENTIONS: After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval. MAIN OUTCOME MEASURES: Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles. RESULTS: Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates. CONCLUSIONS: Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach.
Adult↗