摘要:

Objective:To investigate the effect of the angiotensin converting enzyme (ACE) inhibitor trandolaprilat on vascular smooth muscle cell growth, and to analyse its mechanism of action.Design:Aortic vascular smooth muscle cells (VSMC) from Wistar—Kyoto rats were cultured, and cell proliferation was analysed using a cell synchrony technique.Methods:Proliferative activity was assessed by [3H]-thymidine uptake and doubling time. Protein synthesis was assessed by [3H]-leucine incorporation. Actin formation was measured using sodium dodecylsulphate—polyacrylamide slab gel electrophoresis and a densitometric assay. The effect of trandolaprilat on translational protein synthesis was also examined using the cell-free protein synthesis system of reticulocyte lysate and messenger RNA from VSMC.Results:Trandolaprilat decreased [3H]-thymidine uptake and increased the doubling time of randomly cycling VSMC. The cell synchrony study revealed that this antiproliferative effect was due to increased transition time from S to G2-M. Decreased cell cycle progression during G2-M was reflected by inhibition of cellular protein synthesis during this period. Cellular protein in randomly cycling VSMC was also decreased by trandolaprilat. This decreased protein synthesis was probably produced by inhibition of RNA translation.Conclusions:The ACE inhibitor trandolaprilat reduces VSMC proliferation by lengthening the G2-M phase of the cell cycle, and produces a decrease in cellular protein content. This effect is probably mediated by inhibition of protein synthesis at the translational level.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether induction of arterial hypertension in young normotensive Wistar rats by chronic inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) produced a form of self-sustained hypertension, and to investigate the role of the renin—angiotensin system and vascular hypertrophy in the hypertensive process.Methods:Three-week-old Wistar rats were given 100 or 40mg/kg per day L-NAME or 40mg/kg per day L-NAME plus 100mg/kg per day captopril in their drinking water for between 4 and 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography both during treatment and after the treatment had been stopped. The effect of treatment on plasma renin was measured and the effect of treatment on mesenteric resistance artery structure was determined using a small-vessel myograph.Results:L-NAME produced a progressive and marked increase in blood pressure during the period of treatment. Hypertension was sustained for 14 weeks after stopping treatment. L-NAME resulted in a fourfold increase in plasma renin which remained elevated after treatment was stopped. Blood pressure was correlated with plasma renin levels. Treatment with L-NAME plus captopril markedly attenuated the rise in blood pressure and captopril also produced a marked fall in blood pressure in rats that developed persistent hypertension. Rats with self-sustained hypertension exhibited both cardiac and mesenteric resistance vessel hypertrophy. The induction of vascular hypertrophy with low-dose L-NAME did not result in the development of self-sustained hypertension.Conclusions:Chronic L-NAME treatment in young rats can produce a form of persistent hypertension which is renin-dependent and which does not seem to involve a vascular amplifier mechanism.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:In order to elucidate the role of Na+—Ca2 +exchange in regulating cytosolic free Ca2+concentration in human platelets, we investigated the relationship between cytosolic free Na+and Ca2+concentrations in human platelets.Methods:Sodium-binding benzofuran isophthalate and fura-2 were used to monitor cytosolic free Na+and Ca2+concentrations, respectively.Results:Ouabain at a concentration of 100 µmol/l induced an increase in cytosolic free Na+concentration within 5 min, followed by increases in resting cytosolic free Ca2+concentration and intracellular Ca2+store. These three parameters were increased in a time-dependent manner significantly above the timed control over a period of 60 min. Pre-incubation of platelets with 100 µmol/l ouabain for 30 min significantly enhanced the cytosolic free Ca2+response to thrombin and arginine vasopressin in the absence of extracellular Ca2+. The decrease from peak cytosolic free Ca2+concentration in response to ionomycin in the absence of extracellular Ca2+was significantly slower in low-Na+buffer than in standard buffer. In addition, 5 µmol/l ionomycin increased the cytosolic free Na+concentration markedly in the presence of 0.1 mmol/l extracellular Ca2+, but the rise in cytosolic free Na+concentration was suppressed by 2 mmol/l Ni2+(NiCl2) or by removal of extracellular Ca2+.Conclusions:These results suggest that Na+—Ca2+exchange is important in extruding Ca2+from the cytosol in human platelets, and inhibition of this exchange leads to the accumulation of intracellular Ca2+store, which may be responsible for the enhanced responsiveness of cytosolic free Ca2+to agonists.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The aim of this work was to study the insulin-like growth factor 1 (IGF1), a substance able to promote cell proliferation in vascular smooth muscle, in patients with mild-to-moderate hypertension and to analyse its relationship to sodium—lithium countertransport, a genetic marker of hypertension that is related to cardiovascular complications.Method:We studied 32 hypertensive subjects, some with left ventricular hypertrophy, and 14 healthy subjects. Fasting plasma IGF1 was measured by means of a radioimmunoassay after octadecylsilica chromatography and Na+-Li+countertransport was determined by the method of Canessa.Results:Hypertensive patients had higher values of both IGF1 and Na+-Li+countertransport. We found a positive correlation, irrespective of age, between IGF1 and Na+-Li+countertransport. The patients with left ventricular hypertrophy had significantly higher plasma IGF1 levels than those without left ventricular hypertrophy.Conclusion:Our results confirm a possible role for IGF1 in the cardiovascular complications of hypertension and emphasize its relationship to genetically determined factors.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:To investigate the occurrence of enhanced low-density lipoprotein (LDL) oxidation as an additional factor promoting atherosclerosis progression in hypertensive patients.Design:The oxidation of plasma LDL was investigated in a group of untreated patients with mild-to-moderate essential hypertension without clinically evident target organ damage and in a group of control subjects.Methods:LDL oxidation was evaluated as both the susceptibility to oxidationin vitroand the presence of plasma anti-oxidized LDL antibodies (as an index for oxidationin vivo).Results:LDL from hypertensive subjects exhibited enhanced susceptibility to oxidationin vitroas revealed by early and accelerated generation of conjugated dienes after exposure to CuSO4. Vitamin E concentration in LDL from hypertensive subjects was slightly but significantly decreased and its efficiency in protecting LDL from oxidation was impaired. Furthermore, a higher plasma anti-oxidized LDL titre was found in hypertensive patients. Subclass analysis revealed that the contemporary presence of hypercholesterolaemia did not significantly modify either the increased susceptibility of LDL to oxidation or the presence of plasma anti-oxidized LDL antibodies detected in hypertensive patients. Moreover, no correlation was found between LDL oxidation parameters and blood pressure values.Conclusions:LDL from hypertensive patients is more susceptible to oxidationin vitroand is more promptly oxidizedin vivo. These findings suggest a possible participation of LDL oxidation in promoting and accelerating the atherosclerosis that often develops in hypertensive patients.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The major goals of this study were to determine whether lisinopril and nifedipine lowered blood pressure and improved carotid baroreflexes in older hypertensives.Design:The effects of lisinopril at 10-40 mg/day versus nifedipine gastrointestinal therapeutic system (GITS) at 30-90 mg/day on blood pressure and baroreflex sensitivity were studied after 3 weeks each on (1) single-blind placebo, (2) double-blind assignment to either lisinopril or nifedipine, (3) single-blind placebo, and (4) crossover to double-blind lisinopril or nifedipine. Measurements at the end of the four phases included 24-h blood pressure using the Accutracker, laboratory hemodynamics with the Dinamap and impedance cardiography, baroreflex sensitivity with the pneumatic neck chamber, and plasma samples for neurohumoral and metabolic activity.Patients:Thirteen patients aged 55 years or older (mean ± SEM 65 ± 1 years) with mild-to-moderate hypertension completed the study.Main outcome measures:The primary data for analysis across the four study phases included ambulatory blood pressure values, laboratory hemodynamics, and baroreflex sensitivity.ResultsCompared with the preceding placebo, lisinopril and nifedipine lowered 24-h blood pressure significantly. In the laboratory, the effects of both compounds on blood pressure, cardiac output, calculated total systemic resistance, and the stroke volume—pulse pressure relationship, an index of arterial compliance, were similar. Lisinopril was associated with a relative increase in the standing systolic blood pressure compared with nifedipine (P< 0.05). This coincided with an enhanced heart-rate (R-R interval) response to neck pressure, which also decreased carotid transmural pressure, with lisinopril versus nifedipine (P< 0.05).Conclusions:Lisinopril and nifedipine were both effective as monotherapy for controlling blood pressure in these elderly patients. Despite similar effects on blood pressure and systemic hemodynamics, baroreflex sensitivity in response to a reduction in carotid transmural pressure was greater with lisinopril than with nifedipine.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To assess the relationship of insulin levels and glucose tolerance to blood pressure in hypertension.Design:An open, prospective trial of exercise training with ambulatory blood pressure monitoring and intravenous glucose tolerance testing before and after a 14-week training programme.Patients:Twenty sedentary, untreated, non-obese, normoglycaemic individuals of both sexes with uncomplicated essential hypertension, of whom 16 completed the study.Intervention:Fourteen weeks of supervised, low-intensity, group exercise of three 1-h sessions per week.Main outcome measures:Ambulatory and clinic blood pressure, and glucose and insulin responses to an intravenous glucose tolerance test.Results:Maximal work capacity on a bicycle ergometer increased by 20% (P< 0.001); 24-h ambulatory blood pressure was 143 ± 12/87 ± 5 mmHg before and 142 ± 13/87 ± 7 mmHg after training. Clinic blood pressure decreased from 166 ± 14/103 ± 5 mmHg to 157 ± 12/99 ± 6 mmHg (P< 0.03). Two-way analysis of variance indicated significant decreases in both glucose (P< 0.04) and insulin (P< 0.03), fasting and throughout the intravenous glucose tolerance test.Conclusions:Although mild exercise reduced clinic blood pressure significantly, it did not affect ambulatory blood pressure despite a marked reduction in glucose and insulin levels. This finding argues against a determinant role of insulin in the 24-h maintenance of blood pressure in hypertensive patients under the conditions of the study.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To determine whether the previously reported poor reproducibility of blood pressure variability measured by ambulatory blood pressure monitoring (ABPM) is due to the uncontrolled nature of physical and mental activity during the monitoring period.Design:ABPM was performed on two separate days during which subjects performed identical activities, accompanied by the experimenter. Thus, activity and posture were controlled, both within and between subjects. Two measures of variability were used: SD and the root-mean-square of successive differences (RMSSD).Methods:Thirty-seven subjects participated. Each engaged in a series of activities, such as walking outdoors, editing and alphabetizing tasks, and eating lunch, while wearing an A & D 2420 ambulatory blood pressure monitor which took measurements at 5-min intervals. Measures of variability were computed within each session.Results:Contrary to previous reports, reproducibility was moderately high for blood pressure, with significant correlations between SD and between RMSSD for systolic and diastolic blood pressure. Heart rate reproducibility was less good.Conclusions:Lack of standardization of activities from one occasion to another is a major reason for the poor reproducibility of blood pressure variability when measured using ABPM. Even when activities are standardized, however, the reproducibility of blood pressure variability is still only moderate and may limit the ability of researchers to detect associations between ABPM variability and other measures.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:Evaluation of the prognostic value of 24-h blood pressure averages and 24-h blood pressure variability.Design:After an initial thorough clinical and laboratory evaluation which included 24-h continuous ambulatory blood pressure monitoring, a group of hypertensive patients were re-examined after an average of 7.4 years. End-organ damage at the follow-up visit was related to different measures of blood pressure levels and variability obtained at the initial or the follow-up visit or both.Methods:Seventy-three patients with essential hypertension of variable severity, in whom ambulatory blood pressure was monitored intra-arterially for 24 h (Oxford technique) were re-examined at a follow-up visit (including echocardiographic assessment of left ventricular mass index) 4-13 years later (mean 7.4 years). The severity of end-organ damage was quantified by a score and related to clinic blood pressure at follow-up and to (1) clinic blood pressure, (2) 24-h blood pressure mean, (3) 24-h short-term and long-term blood pressure variability, and (4) end-organ damage, all assessed at the initial visit (multiple regression analysis).Results:The set of independent variables considered was significantly related to end-organ damage at follow-up (R = 0.51). The individual variables most important in determining end-organ damage at follow-up were clinic blood pressure at the follow-up visit (P< 0.01), the initial level of end-organ damage (P< 0.05) and long-term blood pressure variability (among half-hour standard deviation of 24-h mean blood pressure) at the initial evaluation (P< 0.05). The prognostic individual weight of the other haemodynamic parameters considered was less and not statistically significant.Conclusions:The results confirm that the level of blood pressure achieved by treatment and the degree of end-organ damage at the time of initial evaluation are important determinants of future end-organ damage related to hypertension. They also constitute the first longitudinal evidence that the cardiovascular complications of hypertension may depend on the degree of 24-h blood pressure variability.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID