摘要:

Aim of study:Guanine nucleotide regulatory (C) proteins act as key signal transducers for many hormones, growth factors and neurotransmitters, and have been shown to have an important influence on platelet function. As abnormal G-protein levels and activity have been reported in platelets from human non-insulin-dependent diabetics (NIDDM) we studied G-protein function in essential hypertension, a condition which is also associated with insulin resistance and in which abnormal platelet function has been reported.Methods:G-protein function was deduced from studies of adenylyl cyclase activity in platelet membrane preparations from 14 untreated essential hypertensives and 14 controls matched as far as possible for age and sex. Levels of G-protein subunits (Gsα, Giα2and p-subunits) were assessed by immunoblotting, using platelets from 15 subjects with untreated essential hypertension and 15 controls.Results:No changes in levels of G-proteins [Gsα, Giα2and P-subunits) were seen. However, in contrast to the observations in NIDDM, the studies of adenylyl cyclase function identified greater prostaglandin E-|-stimulated activity in hypertensive platelet membranes than in controls (88.8 versus 72% stimulation, P=0.018). This may have a physiological basis in protecting cells against a Ca2+overload.Conclusion: These data are in opposition to the theory that a common defect in G-proteins can explain the association between hypertension and NIDDM.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To assess the effects of angiotensin II on intracellular free Mg2+and Ca2+concentrations in platelets from normotensive and hypertensive subjects.Design and methods:Seventeen normotensive, 25 untreated hypertensive and 18 treated hypertensive patients were studied. Intracellular Mg2 +concentrations were measured with the fluorescent dye mag-fura-2-acetyoxymethylester (AM) and intracellular Ca2+concentrations with the fluorescent dye fura-2AM under basal conditions and after stimulation by angiotensin II, saralasin (angiotensin II antagonist), arginine vasopressin and endothelin-1. The effects of increased extracellular Mg2 +concentrations on intracellular Mg2 +and Ca2+concentrations were also determined.Results:The intracellular basal Ca2+concentration was significantly higher in the untreated hypertensives compared with the normotensives and treated hypertensive subjects (150±14nmol/l versus 120±17nmol/l for normotensives and 124±8nmol/l for treated hypertensives). The basal intracellular Mg2 +concentration was significantly lower in the untreated hypertensive compared to the normotensive and treated hypertensive groups (0.37 ± 0.08 (imol/l versus 0.58 ± 0.09 u.mol/1 for normotensives and 0.52 ±0.11 u.mol/1 for treated hypertensives). In the hypertensive group, inverse correlations were found between intracellular Ca2+and intracellular Mg2 +concentrations (r=-0.44, P < 0.05) and between intracellular Mg2 +and diastolic blood pressure (r=—0.35, P < 0.05), while a positive correlation was found between intracellular Ca2+and systolic blood pressure (r=0.41, P < 0.05). Exposure of the platelets to 1 nmol/l angiotensin II significantly increased intracellular Ca2+and significantly decreased intracellular Mg2 +concentrations in all three groups. The angiotensin ll-evoked effect on intracellular Ca2+was exaggerated in the untreated hypertensives and blunted in the treated patients (basal versus stimulated: 150±14 versus 217±20nmol/l in untreated hypertensives; 124±8 versus 140±10nmol/l in treated hypertensives). Saralasin (0.1 u,mol/l) abolished the effects of angiotensin. Arginine vasopressin (1 u,mol/l) increased the intracellular Ca2+concentration, whereas endothelin-1 (1 nmol/l) had no significant effect on either intracellular Ca2+or intracellular Mg2 +. Increasing extracellular Mg2 +concentrations led to significant reductions in intracellular Ca2+concentrations in all groups and a significant elevation of the intracellular Mg2 +concentration in the untreated hypertensive patients only.Conclusions:These data demonstrate a relationship between angiotensin II and intracellular magnesium and calcium. In hypertension, angiotensin ll-stimulated calcium responses may be related to simultaneously decreased intracellular magnesium concentrations.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Aim:To compare the effects of an angiotensin converting enzyme (ACE) inhibitor and a thiazide diuretic on platelet function and haemorrheological variables, since these factors may contribute to the atherosclerotic and thrombotic complications associated with hypertension.Methods:Following a 2-week placebo period, 80 male and female patients with mild to moderate hypertension, aged 50±10 (mean±SD) years, were randomly allocated in a double-blind study to 4 weeks of treatment with the ACE inhibitor lisinopril at 20 mg once a day or the diuretic hydrochlorothiazide at 25 mg once a day. Venous blood was sampled before and at the end of the 4-week treatment period to assess platelet function and haemorrheological variables.Results:Both treatments lowered systolic and diastolic blood pressure equally and had no significant effect on platelet counts and platelet aggregation in response to ADP and to arachidonic acid. Haematocrit plasma viscosity and blood filterability were not altered by either drug. Hydrochlorothiazide tended to increase and lisinopril tended to decrease whole blood viscosity at all shear rates but these changes did not reach statistical significance.Lisinopril increased the erythrocyte aggregation time (from 1.98 ±0.50 to 2.08 ± 0.52 s) and decreased the disaggregation shear rate (from 159 ±46 to 153±40s˜1) and the disaggregation shear stress (from 705 ±257 to 659±204mPa). Hydrochlorothiazide induced the opposite effects (2.00±0.47 to 1.92±0.39s, 181 ±531 to 196±82s~1 and 813 ±268 to 868±392mPa, respectively) with a statistically significant (P < 0.05) intergroup difference.Conclusions: These findings suggest that chronic treatment with the ACE inhibitor lisinopril, but not the diuretic hydrochlorothiazide, may produce favourable effects on blood rheology, but the clinical relevance requires further investigation.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:The present study examines the effect of angiotensin converting enzyme inhibition on the renal haemodynamic and sodium excretory responses to noradrenaline in man.Design:We studied the effects of intravenous noradrenaline (0.075 (J.g/kg per min) and enalapril pretreatment (5 mg/day for 5 days), alone and in combination, on urinary sodium excretion, effective renal plasma flow, glomerular filtration rate and segmental tubular function in nine normal subjects.Methods:The subjects were studied during maximal water diuresis. The clearance of inulin and of para-aminohippurate were used to estimate the glomerular filtration rate and effective renal plasma flow, respectively. Segmental tubule handling of sodium was assessed by the lithium clearance method.Results:Noradrenaline alone decreased urinary sodium excretion (P<0.01) and the effective renal plasma flow (P<0.01) without altering the glomerular filtration rate. Enalapril pretreatment significantly attenuated this fall in sodium excretion (P<0.05) and effective renal plasma flow (P<0.05), and had a similar attenuating effect on the noradrenaline-induced decrease in the fractional excretion of lithium. The pressor response to noradrenaline infusion was not, however, influenced by the enalapril pretreatment.Conclusions:Enalapril blunts the renal vasoconstrictive effect and the antinatriuretic effect of noradrenaline in man. Our results indicate that there is an important interaction between the sympathetic nervous system and the renin-angiotensin system in the kidneys in man.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objectives:To compare the reproducibility of clinic and ambulatory blood pressure measurements in elderly hypertensive subjects.Subjects:Twenty-two untreated elderly hypertensives, with a clinic systolic blood pressure (SBP) > 160mmHg and/or diastolic blood pressure (DBP) > 95mmHg, and a mean age of 76 years (range 66-86).Methods:Following three supine clinic blood pressure readings the subjects underwent 24-h non-invasive ambulatory blood pressure monitoring, measurements being taken at 20-min intervals from 0700 to 2200 h and at 30-min intervals from 2200 to 0700 h. Measurements were repeated during a further visit at a median interval of 10 weeks (range 1—10 months).Results:Daytime ambulatory SBP levels were 20mmHg (95% confidence interval 14-27 mmHg, P<0.001) lower than clinic SBP, although DBP values were similar. The mean 24-h ambulatory SBP and DBP reproducibility [assessed by the standard deviation of differences (SDD) between visits] was significantly better than that for mean clinic blood pressure (SBP 6.3 versus 17.4 mmHg, P<0.001; DBP 4.8 versus 7.0 mmHg, respectively, P<0.05). With daytime defined as 1000-1959 h, the SDD between visits was 12.4 mmHg for SBP and 8.3 mmHg for DBP, but with daytime defined as 0700-2159 h, the SDD fell to 6.0 mmHg for SBP and 4.8 mmHg for DBP, values almost identical to those obtained with full 24-h blood pressure monitoring. There was no difference in night-time blood pressure reproducibility, whether night-time was defined as 2400-0559 h or 2200-0659 h.Conclusions:Both 24-h and daytime ambulatory blood pressure monitoring significantly improve the reproducibility of blood pressure measurements compared with clinic blood pressure readings in elderly hypertensive subjects. Increasing the number of daytime blood pressure readings by 50% (from 30 to 45) reduced the variability of blood pressure measurement by 50%. Twenty-four-hour ambulatory blood pressure monitoring is of value in obtaining reproducible blood pressure measurements in elderly hypertensive subjects. However, more than 30 readings are needed during a daytime recording to significantly reduce variability compared with repeated clinic measurements, although night-time variability is not significantly affected if the number of readings is reduced to 12 over a 6-h period.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To elucidate distinctive patterns of circadian variation of blood pressure in diabetic patients.Design:Circadian variations and indices of blood pressure variability were examined by non-invasive ambulatory blood pressure monitoring. The indices were assessed for a correlation with various possible signs of autonomic neuropathy, including the coefficient of variation of the RR interval and orthostatic hypotension.Methods:The study was conducted on 38 normotensive diabetics and 15 age- and sex-matched non-diabetic controls, all of whom were outpatients at the Third Department of Internal Medicine in Nagoya University Hospital. Ambulatory blood pressure measurements were taken in all subjects and the coefficients of variation in the RR interval and postural changes in blood pressure were determined.Results:The diabetic patients demonstrated a different pattern of circadian variation in blood pressure from that of the non-diabetics. Diurnal-nocturnal differences were significantly smaller in diabetics than in non-diabetic controls. Statistically significant correlations were found between diurnal-nocturnal differences in blood pressure and the duration of diabetes, glycaemic control, the coefficient of variation in the RR interval and the change in blood pressure on standing. A subgroup of diabetic patients with severe autonomic neuropathy showed the lowest diurnal—nocturnal differences.Conclusions:In diabetic patients with autonomic neuropathy circadian variations in blood pressure are blunted. Ambulatory blood pressure monitoring can detect these abnormal variations and therefore may be useful in evaluating diabetic autonomic neuropathy.

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Long-term exposure to high concentrations of lead may adversely affect several organ systems, but the possible influence of low-level lead exposure on blood pressure remains debatable. The present study examined this relationship in a cross-sectional population survey.Methods:Blood pressure and lead exposure were measured in 1648 subjects (827 males, 821 females; mean age 45 years), drawn at random from the general population, but not being treated for hypertension.Results:Systolic/diastolic blood pressure averaged 131/77 mmHg in the males and 124/74 mmHg in the females. Blood lead was higher in males than in females (0.5 versus 0.3µu,mol/l), but the opposite was observed for zinc protoporphyrin (1.0 versus 1.1µg /g haemoglobin). After adjustment for significant covariates (age, body mass index, pulse rate, serum creatinine and serum calcium, and for contraceptive pill intake and menopause in females), systolic pressure was negatively correlated with blood lead in males; the partial correlations with blood lead were not significant for systolic pressure in females nor for diastolic pressure in either sex. Neither males nor females showed a significant relationship between blood pressure and lead exposure assessed from the zinc protoporphyrin level in blood.Conclusions:This study does not support the hypothesis exposure to lead is associated with increased blood pressure in the population at large that ex exposure to lead is associated with increased blood pressure in the population at large

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID