Estrogen stimulation of plasma renin substrate (PRS) was studied in men with alcoholic cirrhosis. PRS values, before and 1, 2, 4 and 6 days after a single oral administration of 100 .mu.g of an estrogen derivative, **...
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Estrogen stimulation of plasma renin substrate (PRS) was studied in men with alcoholic cirrhosis. PRS values, before and 1, 2, 4 and 6 days after a single oral administration of 100 .mu.g of an estrogen derivative, ***.-methoxy-17-ethynyl-1,3,5(10)-estratriene-3,***.-diol (Moxestrol), were measured by radioimmunoassay of generated angiotensin I in 5 men with normal liver function and 5 men with alcoholic cirrhosis. Basal PRS was 0.93 .+-. 0.22 nmol/ml in the normal men and significantly lower (P < 0.01) in the men with cirrhosis (0.33 .+-. 0.14 nmol/ml). Two days after administration of Moxestrol, PRS rose significantly but transiently (P < 0.05) to 1.41 .+-. 0.42 nmol/ml in the normal men and to 0.47 .+-. 0.15 in the cirrhotic men, the relative increase (.apprx. 50%) being similar in both groups. A study of the plasma kinetics and urinary excretion of Moxestrol was also performed to evaluate its metabolic clearance rate and absorption. Since the intestinal absorption of [14C]Moxestrol was not depressed in cirrhotic men, the low PRS values recorded are probably the consequence of hepatocyte dysfunction.
Background Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen ...
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Background Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects. Methods and Results This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 +/- 3.9 nmol/L;1 allele, 15.7 +/- 5.1 nmol/L;2 alleles, 17.3 +/- 4.7 nmol/L;P = .006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P = .001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents (P < .05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5;95% confidence intervals 1.1 to 2.1, P = .03, and 1.0 to 2,1, P = .05, respectively). Conclusions The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.
The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At p...
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The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropyl-fluorophosphate (DFP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet has been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity.
To dissect the genetic pathway of hypertension, we measured angiotensinogen in 685 members of 186 families recruited from a rural community in southwest Nigeria. Commingling and segregation analyses were carried out. ...
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To dissect the genetic pathway of hypertension, we measured angiotensinogen in 685 members of 186 families recruited from a rural community in southwest Nigeria. Commingling and segregation analyses were carried out. A mixture of two and/or three distributions fits the data significantly better than a single distribution in commingling analysis, suggesting a major gene effect. Segregation analysis confirmed that a recessive major gene model for low values of angiotensinogen provides the best fit to the data and about 13% of the variance was due to the recessive gene segregation.
Objective To compare the angiotensinogen genotypes in normotensive and pre-eclamptic pregnancies in maternal and fetal samples. Design Prospective observational study. Setting University Hospital, Queen's Medical ...
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Objective To compare the angiotensinogen genotypes in normotensive and pre-eclamptic pregnancies in maternal and fetal samples. Design Prospective observational study. Setting University Hospital, Queen's Medical Centre Nottingham. Population Forty-three women with pre-eclampsia and 84 normotensive pregnant women. Fetal samples were available for genotyping from 96% of the pregnancies. Methods Maternal and fetal DNA was genotyped at angiotensinogen codon 235 and at a dinuclcotide repeat polymorphism in the 3' flanking region of the gene. Angiotensinogen and renin concentrations were measured in maternal plasma by radioimmunoassay. Results In contrast to earlier studies, no association was demonstrated between the angiotensinogen 235 and variant and pre-eclampsia. Normotensive pregnant women homozygous for this variant had significantly lower plasma angiotensinogen concentrations (median 2.2 ng Al/mL;IQR 1.8-3.0) than women homozygous for the 235 Met allele (3.6 ng Al/mL: IQR 2.5-4.1;P = 0.04). In pre-eclamptic pregnancies, 79% (11/14) of mothers heterozygous for the dinucleotide repeat allele designated A9 transmitted this allele to the fetus, more frequently than would be expected by chance (P = 0.02). The A9 allele was associated with low plasma angiotensinogen concentrations (P = 0.001) and high renin concentrations (P = 0.02) in normotensive women. Conclusions There is no evidence that the angiotensinogen 235 Thr allele is associated with pre-eclampsia in the Nottingham population. The angiotensinogen 235 Thr allele is associated with low plasma angiotensinogen concentrations in normotensive pregnant women, in contrast to the high levels associated with this variant in non-pregnant women suggesting that regulation of angiotensinogen expression in normal pregnancy may differ significantly from that in the non-pregnant state. There is preliminary evidence that maternal-fetal transmission of an angiotensinogen allele associated with low plasma angiotensinogen conce
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