摘要:

ObjectiveTo determine the effects of angiotensin II (AII) (1–8) on cytosolic free calcium concentrations in the absence and in the presence of the selective angiotensin subtype 1 (AT1) receptor antagonist losartan and of the selective angiotensin subtype 2-receptor antagonist P-186 in human peripheral blood mononuclear cells (PBMC). We also assessed the effect of the AII analogues AII (2–8), AII (3–8) and AII (4–8) on the cytosolic free-calcium concentration in human PBMC.MethodsThe cytosolic free-calcium concentration was assayed in human peripheral blood mononuclear cells by measuring the fluorescence of fura-2 entrapped by these cells.ResultsAdministration of AII caused a concentration-dependent increase in the cytosolic free-calcium concentration in human peripheral blood mononuclear cells with a half-maximal increase at 5 × 10−8mol/l. Also administration of the heptapeptide AII (2–8) increased the intracellular free-calcium concentration in human PBMC, whereas AII (3–8) and AII (4–8) had no effect. The AII (1–8)-induced rise in cytosolic free-calcium concentration was blocked completely by losartan but not by P-186.ConclusionOur data demonstrate that the effects of AII on the cytosolic free-calcium concentration in human PBMC are AT1receptor-mediated since they were abolished by the specific AII AT1receptor antagonist losartan but not by the specific angiotensin subtype 2 receptor antagonist P-186.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundWe had observed previously that the aldosterone excretion rate and plasma aldosterone concentration were lower for black children than they were for white children. We did not know whether this was secondary to a lower intake of potassium or to suppression of the renin–angiotensin system in blacks.ObjectiveTo test the hypothesis that the secretion of aldosterone in response to potassium would be different in blacks than in a control group of whites.DesignBlack and white subjects were selected on the basis of their having aldosterone excretion rates that were in the lowest quartile for the entire original cohort. Since the blacks typically had lower aldosterone excretion rates than did the whites, the black participants were represented primarily by those with average rates of aldosterone production among blacks, whereas the whites were represented by those with the lowest aldosterone production rates among whites. The protocol consisted of a placebo-controlled, randomized cross-over study design.MethodsTwelve blacks and 12 whites, aged 14.1 ± 1.6 (mean ± SD) and 15.4 ± 2.1 years, respectively, were allocated randomly to double-blind treatment either with placebo or with 40 μmol/day potassium chloride for 7 days and then the alternate treatment. Measurements of the plasma renin activity (PRA), plasma aldosterone concentration, and urinary aldosterone excretion were performed in an inpatient research unit at the end of the treatment. The blood pressure was monitored for 24 h.ResultsTreatment with potassium increased the plasma aldosterone concentration (P= 0.0006) and the urinary excretion of aldosterone (P= 0.0002) significantly both for blacks and for whites. There was no significant racial difference in the response to potassium. The PRA was overall 1.605-fold lower in the blacks than it was in the whites (P= 0.0124). The lowest PRA levels, such as those in the blacks when they were supine, tended to be increased with the potassium treatment. The blood pressure did not change significantly with the potassium supplement for either racial group.ConclusionsAfter we had supplemented the intake of potassium, aldosterone production increased in the blacks and in the control group of whites to the same extent. The potassium treatment appeared to increase lower PRA levels. A lower intake of potassium could at least partially account for the suppression of the renin–aldosterone system in blacks.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo study the cross-sectional relationship between circulating angiotensin converting enzyme (ACE) activity and echocardiographically determined left ventricular geometry in a study of 380 70-year-old men participating in a health-survey reexamination and 50 patients with hypertension.MethodsTwo-dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of serum ACE activity.ResultsThe serum ACE activity was higher in the elderly men with left ventricular concentric hypertrophy than it was in men with normal geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l, respectively,P< 0.01 for both comparisons before and after adjustment for the 24 h mean arterial pressure, body mass index, and use of antihypertensive medication). The serum ACE activity correlated with the thickness of the left ventricular interventricular septum (r = 0.12,P= 0.0095), the left ventricular relative wall thickness (r = 0.13,P= 0.0053), and the total peripheral resistance (r = 0.16,P= 0.0034), but not with the left ventricular mass (r = −0.039,P= 0.45) of these elderly men. The serum ACE activity in the hypertensive patients also correlated with the left ventricular interventricular septum thickness (r = 0.34,P= 0.020) independently of the 24 h mean arterial blood pressure, age, sex, body mass index, and insulin sensitivity.ConclusionLevels of serum ACE activity are associated with left ventricular geometry.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundPhosphatidylinositol 3-kinase phosphorylates membrane lipids at the third position of the inositol ring producing phosphoinositides, not on the pathway for production of 1,4,5-triphosphate.ObjectiveTo test the hypotheses that angiotensin II (Ang II) activates phosphatidylinositol 3-kinase in cardiomyocytes and that this pathway is involved in Ang II-induced protein synthesis.MethodsCardiomyocytes, in culture, from 7-day-old chick embryonic hearts were treated with Ang II and the activation of phosphatidylinositol 3-kinase was assessed after immunoprecipitation with antibodies to the p85 subunit of phosphatidylinositol 3-kinase by the conversion of PI (phosphatidylinositol) to phosphatidylinositol 3-monophosphate (PIP) in the presence of g-[32P]-ATP and analyzed by thin-layer chromatography. Western blotting was performed after antiphosphotyrosine immunoprecipitation with antibodies to the p85 subunit of phosphatidylinositol 3-kinase. Protein synthesis was assessed by [35S]-methionine incorporation and polyacrylamide gel electrophoresis.ResultsAng II stimulated phosphatidylinositol 3-kinase activity dramatically, with 4.5- and 3.5-fold increases in PIP formation after 1 and 5 min, respectively. The involvement of tyrosine kinases was demonstrated by Western blotting in which Ang II increased tyrosine phosphorylation of a protein recognized by antibodies to the 85 kDa subunit of phosphatidylinositol 3-kinase. Furthermore, the tyrosine kinase inhibitor lavendustin A blocked Ang II-stimulated phosphatidylinositol 3-kinase activity and conversion of phosphatidylinositol to PIP. Ang II increased new protein synthesis as reflected by the significantly (P< 0.05) greater incorporation of [35S]-methionine into cardiomyocytes treated with Ang II. The link between Ang II and protein synthesis was mediated in part through phosphatidylinositol 3-kinase because the phosphatidylinositol 3-kinase inhibitor wortmannin blocked the effect of Ang II on protein synthesis. Increased production both of nuclear and of cytosolic proteins was demonstrated by agarose gel electrophoresis of these cellular components of Ang II-treated cardiomyocytes. Wortmannin produced a general inhibition of the synthesis of nuclear and cytosolic proteins, with a greater effect on nuclear proteins. The action of wortmannin on nuclear protein synthesis was confirmed by similar findings with another phosphatidylinositol 3-kinase inhibitor, LY294002.ConclusionPhosphatidylinositol 3-kinase activation by Ang II occurs through a pathway utilizing tyrosine phosphorylation. Furthermore, this pathway is involved in cardiomyocyte protein synthesis and the possibility that it is operative in Ang II-mediated cardiac hypertrophy arises.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo establish the role played by the circulating nitric oxide synthase inhibitorsNG-monomethyl-L-arginine (L-NMMA), asymmetrical dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) and its association with hypertension of children and adolescents.DesignWe measured plasma concentrations ofL-NMMA, ADMA and SDMA in 38 hypertensives (median age 7.7 years) and in nine healthy normotensive controls (median age 8.2 years) using high-performance liquid chromatography. In addition, their plasma renin activity was determined. The subjects' glomerular filtration rates were calculated from plasma creatinine and height measurements. To determine the vasoactive potency of the arginine analogues, concentration–response curves were plotted for the responses in isolated endothelium-intact and endothelium-denuded mouse aortic rings that had been pre-contracted by administration of a threshold concentration of phenylephrine.ResultsPlasma ADMA and SDMA concentrations in members of the hypertensive group [0.23 ± 0.03 and 1.37 ± 0.06 μmol/l, respectively (means ± SEM)] were significantly higher than those in members of the control group (ADMA 0.10 ± 0.01 μmol/l and SDMA 1.18 ± 0.06 μmol/l). Plasma concentrations ofL-NMMA were similar in members of the hypertensive (0.21 ± 0.01 μmol/l) and control (0.18 ± 0.02 μmol/l) groups. The glomerular filtration rate of the hypertensive group was below normal [70.4 ± 5.4 ml/min per 1.73 m2(mean ± SEM)] and was significantly associated with elevated plasma concentrations of ADMA (r = −0.77,P< 0.001), SDMA (r = −0.38,P= 0.02) andL-NMMA (r = 0.35,P= 0.03). Higher plasma ADMA concentrations were associated with a lower plasma renin activity (r = −0.36,P= 0.04). The vasoactive potencies of ADMA (concentration for half-maximal effect with the endothelium intact 25.4 ± 7.1 μmol/l) andL-NMMA (concentration for half-maximal effect with the endothelium intact 8.2 ± 2.9 μmol/l) was significantly (P< 0.05) greater than that of SDMA. Both ADMA andL-NMMA (at 3 μmol/ l concentrations) initiated a significant vasocontractile response from baseline (P= 0.03 andP< 0.001, respectively). These effects were absent after the endothelium had been removed. SDMA had no effect.ConclusionsPlasma ADMA and SDMA levels are increased in hypertensive children. By inference from in-vitro data, ADMA appears to attain sufficient concentrations to produce a significant change in vascular tone and hence might play a role in the pathophysiology of childhood hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID