摘要:

ObjectiveTo determine whether stretch-activated cation channels (SAC) are present in intact human umbilical vein endothelium (HUVE) and in an endothelial cell line (EA.hy) and whether they act as endothelial mechanosensors, and to determine whether endothelial SAC in HUVE from women with pregnancies complicated by preeclampsia undergo functional changes compared with those in HUVE from women with normotensive pregnancies.Methods and resultsBy use of the patch-clamp technique we identified a SAC in intact HUVE and in an endothelial cell line. The SAC had mean conductances of 29 ± 5 pS (n= 38) for K+and 12 ± 2 pS (n= 4) for Ca2+. Administration of 50 μmol/l gadolinium, a blocker of mechanosensitive ion channels, completely blocked activity of this channel. We found from single-channel recordings that influx of Ca2+through SAC directly activated high-conductance Ca2+-dependent potassium channels, proving that a significant influx of Ca2+through SAC occurs at physiologic concentrations of Ca2+. In a comparative study, apparent channel density of SAC (percentage of patches with SAC activity) in HUVE from women with pregnancies complicated by preeclampsia (36.2 ± 4.3%) was twofold higher than that in HUVE from women with normal pregnancies (17.9 ± 2.9%,P< 0.01). Channel conductance and sensitivity to stretching of SAC were not altered by preeclampsia.ConclusionsSince SAC are capable of acting as endothelial mechanosensors, the greater than normal density of SAC associated with preeclampsia might reflect an alteration of mechanotransduction.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundPatients with Cushing's syndrome exhibit a bimodal distribution of maximal rates of the erythrocyte amiloride-sensitive Na+/H+exchange (NHE). Enhanced erythrocyte NHE has recently been found in patients with primary aldosteronism.ObjectiveTo test the hypothesis that occult hypermineralocorticoidism in a subset of patients with Cushing's syndrome is responsible for the greater than normal NHE.MethodsNHE was measured as maximal initial rate (Vmax) of amiloride-inhibited efflux of H+into an alkaline Na+-containing medium, for 47 patients with hypercortisolism (20 with pituitary adenomas, 18 with adrenal adenomas, and nine with ectopic production of adrenocorticotropin). Clinical appearance, blood pressure levels, plasma aldosterone and deoxycorticosterone levels, serum electrolytes, and urine (tetrahydrocortisol plus 5-α-tetrahydrocortisol): tetrahydrocortisone ratios were assessed for all patients. Twenty patients (10 with greater than normal NHE and 10 with low-to-normal NHE) were randomly selected from 47 patients with hypercortisolism, and treated with 200 mg/day spironolactone for 7 days. NHE in these patients was assessed before starting the treatment and 2 days after its cessation.ResultsGreater than normal NHE (Vmax) was associated with peripheral edema, high diastolic blood pressure, hypokalemia, and high urine (tetrahydrocortisol plus 5-α-tetrahydrocortisol): tetrahydrocortisone ratios. The enhanced NHE was rapidly normalized by treatment with spironolactone.ConclusionErythrocyte NHE in patients with hyper-cortisolism and functional hypermineralocorticoidism is greater than normal due to incomplete peripheral conversion of cortisol (which binds to mineralocorticoid receptors) into metabolically inactive cortisone.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundProduction of heat shock protein 70 (HSP70) in the heart is induced by hemodynamic stress, but its intracellular signal transduction system has not been elucidated well.ObjectiveTo investigate the hypothesis that protein kinase A (PKA)-dependent and protein kinase C (PKC)-dependent systems are involved in the pressure-induced expression of HSP70 mRNA in perfused adult rat heart.MethodsIsolated tetrodotoxin-arrested Sprague–Dawley rat hearts were perfused as Langendorff preparations at a constant aortic pressure of 60 mmHg. Aortic pressure in rats of the pressure-overloaded group was elevated from 60 to 120 mmHg for 2–120 min. cAMP contents and rates of synthesis of protein were measured by radioimmunoassay and the incorporation of [14C]phenylalanine into total heart protein, respectively. Expression of HSP70 mRNA was determined by Northern blot analysis.ResultsElevation of aortic pressure significantly increased cAMP content after 2 min of perfusion (by 41%), significantly increased rates of synthesis of protein during the second hour of perfusion (by 41%), and induced expression of HSP70 mRNA maximally after 60 min of perfusion (2.7-fold the control value). Exposure to glucagon, forskolin or 1-methyl-3-isobutylxanthine mimicked increases in these parameters caused by elevation of aortic pressure. Administration of a selective PKA inhibitor, H-89, significantly prevented induction of increases in expression of HSP70 mRNA and rates of synthesis of protein by a high pressure overload and exposure to agents that increase cAMP content. Furthermore, administration of phorbol ester induced expression of HSP70 mRNA. Administration of a PKC inhibitor, calphostin C, significantly prevented induction of increases in expression of HSP70 mRNA by a pressure overload and by exposure to phorbol ester.ConclusionsThese results suggest that the pressure-induced induction of production of HSP70 is regulated both by PKA-dependent and by PKC-dependent systems during periods of active synthesis of protein in adult rat heart.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo compare the calculations of left ventricular mass according to thick-wall [American Society of Echocardiography (ASE) and Penn convention] and thin-wall (Wikstrand formula) models.MethodsWe have reexamined the data from the cross-sectional study on the general population sample of Vobarno and from a prospective longitudinal study of hypertensive patients assessing the prognostic significance of changes in left ventricular mass during a follow-up period of 10 years on average (Brescia population).ResultsFor the Vobarno and Brescia populations, we found a close relationship between values of left ventricular mass calculated by using a thin-wall ellipsoidal model (Wikstrand formula) and those calculated using a thick-wall model with Penn convention or ASE left ventricle measurements (r= 0.99, for both the Vobarno and Brescia populations). Highest values of Penn left ventricle mass were slightly underestimated by use of the thin-wall formula.The numbers of nonfatal cardiovascular events and the relative risks, evaluated by Cox proportional hazard models for 151 patients seen at follow-up did not differ for patients with persistence of left ventricular hypertrophy (LVH), those with regression of LVH, and those with normal left ventricle mass, both at baseline and at follow-up, when these different ways of measuring left ventricle mass and partition values for LVH were used.ConclusionsThe calculation of left ventricle mass according to the ASE recommendations or to the Penn convention, both of which are based on the assumption that the left ventricle can be represented by a prolate ellipsoid with both the internal and external long axes twice the short axis, produces results similar to those obtained using an alternate formula for the calculation of left ventricle mass, considering wall thickness constant around the ellipsoidal cavity. The cardiovascular risk stratification, in relation both to baseline left ventricular mass and to its change during long-term antihypertensive treatment, does not differ significantly among the results of these three different calculations.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundM-mode echocardiographic left ventricular mass calculated using a thick-wall prolate ellipsoidal model is widely used in clinical and epidemiologic studies. Doubts regarding the ability of this approach to obtain a precise estimate of left ventricular weight across a wide range of values have recently been raised and an alternate thin-wall ellipsoidal model has been proposed to gain greater precision.ObjectiveTo compare thin-wall and thick-wall (American Society of Echocardiography and Penn convention) models for calculation of left ventricular mass.DesignValidation, cross-sectional, and longitudinal studies.ParticipantsNecropsy data and living cohorts from Naples, New York City, and Umbria region of Italy (PIUMA registry).ResultsThe average thin-wall left ventricular mass was slightly greater than the necropsy left ventricular weight (mean 225 versus 220 g), whereas no difference was detected using regression-adjusted thick-wall methods. Use of the thin-walled model slightly overestimated left ventricular mass relative to both thick-wall models at the lowest left ventricular mass while slightly underestimating the highest values. Comparison of Cox proportional hazard models in two longitudinal studies demonstrated that there was a substantial equivalence among methods, with a marginally better performance of thick-wall models for cardiovascular risk stratification (P< 0.05 in one study).ConclusionsAlthough it is imperfect, because it is based on simplifying geometric assumptions, computation of left ventricular mass on the basis of M-mode echocardiographic left ventricular dimensions using thick-wall prolate-ellipsoidal models is valuable for identification of left ventricular hypertrophy and for cardiovascular risk stratification of patients with essential hypertension. Calculation of left ventricular mass by use of a thin-wall prolate-ellipsoidal geometry does not yield appreciably different results than those which are obtained by use of thick-wall models.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID