ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo study the effects of the selective neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 in spontaneously hypertensive rats (SHR) in order to elucidate whether NPY function may be altered in the SHR and whether the NPY Y1 receptor plays a specific role in the maintenance of high blood pressure in this genetic form of hypertension.MethodsPithed and conscious SHR were studied after intravenous administration of 0.125–1 mg/kg BIBP 3226. The cardiovascular effects were evaluated under baseline conditions, under acute stress and after exogenous administration of 20 μg/kg NPY. The potentiating effects of NPY on pressor responses to phenylephrine and tyramine were studied in the SHR.ResultsIntravenous administration of 0.125–1 mg/kg BIBP 3226 dose-dependently inhibited the pressor response to exogenous NPY in pithed SHR. At higher doses BIBP 3226 had an effect duration of 20–40 min. In the pithed SHR, a 0.5 mg/kg bolus injection of BIBP 3226 shifted the pressor response curve for exogenous NPY significantly to the right. It also inhibited significantly the potentiating effects of NPY on pressor responses to phenylephrine and tyramine. In conscious SHR, 0.125–1 mg/kg BIBP 3226 did not reduce the basal blood pressure. In combination with a hypotensive dose of prazosin, administration of 0.5 mg/kg BIBP 3226 had no added effects lowering the basal blood pressure. A stressful stimulus, namely an air jet, caused a brief increase in blood pressure and heart rate in the conscious SHR. In this model, 0.5 mg/kg BIBP inhibited the heart rate response slightly but had no effect on the blood pressure response.ConclusionsOur results demonstrate that, although the selective NPY Y1 receptor antagonist BIBP 3226 may shift the pressor response to exogenous NPY potently, it does not influence basal blood pressure significantly in the SHR.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine the prevalance of enhanced signal transduction in immortalized B lymphoblasts from normotensive subjects and patients with essential hypertension.MethodsWe established Epstein-Barr virus-immortalized lymphoblast cell lines from 26 normotensive and 37 hypertensive subjects. Subsequently, we quantified rises in the cytosolic free Ca2+concentration, [Ca2+]i, evoked by 0.1 μmol/l platelet-activating factor (PAF) in Fura-2- loaded cells.ResultsPAF-induced [Ca2+]irises were independent of donor age in cells from normotensive and hypertensive subjects. Baseline values of [Ca2+]iwere not significantly different in the two groups. Using the mean + 2SD of the PAF-evoked rises in [Ca2+]iabove basal (110 nmol/l) as the upper normal value, we estimate that enhanced [Ca2+]irises are distinctly more prevalent in hypertensive subjects (27%) than they are in normotensive subjects (4%). Similarly, upon definition of normal values by the 99% confidence interval (75 nmol/l), 19% of cells from normotensive versus 43% from hypertensive subjects display enhanced intracellular signaling.ConclusionEnhanced intracellular signal transduction could be the primary defect in approximately one-third of the overall population with essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundWe examined the relation between cardiovascular reactivity (the response of the cardiovascular system to psychological stress) and the severity and progression of carotid atherosclerosis.MethodsUsing duplex ultrasonography, we measured the change in the area of all detectable plaques in the extracranial carotid arteries during 2 years. Cardiovascular reactivity was assessed by measuring changes in hemodynamics during a frustrating cognitive task (the Stroop Color Word Interference Task). Established risk factors for atherosclerosis were measured by interviewing patients, a physical examination, and blood assays for 351 subjects with a wide range of types of atherosclerotic disease.ResultsAtherosclerotic plaques were present in the carotid arteries of 273 (78%) subjects. In a forward stepwise multiple regression analysis, it was found that greater age (β = 0.46), a history of hypertension (β = 0.20), use of lipid level-lowering agents (β = 0.18), a longer history of smoking (β = 0.13), a larger cholesterol: high-density lipoprotein ratio (β = 0.13), a smaller change in heart rate during the task (β = −0.12), and a higher resting systolic blood pressure (SBP; β = 0.11) were associated significantly with a greater plaque area (R2= 0.35). In 136 untreated subjects who were followed up for 2 years, a greater change in SBP during the task (b = 0.28), a higher total cholesterol: high-density lipoprotein ratio (β = 0.23), a shorter resting preejection period (β = −0.19), and a lower body mass index (β = −0.17) were significant predictors of the change in atherosclerosis, after controlling for age and initial plaque area in a stepwise multiple regression analysis (R2= 0.24).ConclusionsThese results support the hypothesis that hemodynamic responses under conditions of mental stress may influence the progression of atherosclerosis.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundEndothelins are potent vasoconstrictors, and may also act as mitogens and hypertrophic agents. Expression of a member of this family of peptides, endothelin-1, is enhanced in the endothelium of blood vessels of rats with severe forms of hypertension, even in the absence of elevated plasma endothelin levels. In some of these hypertensive models enhanced endothelin-1 gene expression may contribute to vascular hypertrophy of small arteries and to elevation of blood pressure.ObjectiveTo establish whether endothelin-1 may play a role in essential hypertension in humans, in whom plasma levels are known to be usually within normal limits, by examining the expression of the endothelin-1 gene in resistance-size arteries of normotensive subjects, and in humans with mild and severe hypertension.MethodsUsing in-situ hybridization, the abundance of endothelin-1 messenger RNA transcripts was evaluated in small arteries of subcutaneous gluteal fat obtained by biopsy in normotensive and hypertensive patients.ResultsVessels from five normotensive subjects and four untreated mild essential hypertensive patients did not exhibit topographically localized specific labeling with the antisense human endothelin-1 probe. Biopsies from four untreated hypertensive patients with moderate-to- severe blood pressure elevation, in contrast, showed a heavy density of grains on endothelial cells of small arteries of gluteal subcutaneous fat, corresponding to hybridization of the antisense human endothelin-1 complementary RNA probe with endothelin-1 messenger RNA.ConclusionSome patients with moderate-to-severe essential hypertension, similar to some experimental rat models with severe blood pressure elevation, exhibit enhanced endothelial expression of the endothelin-1 gene. This is the first demonstration that overexpression of the endothelin-1 gene may occur in the vascular wall in a small sample of this subset of hypertensive patients. This pathophysiologic phenomenon could play a role in blood pressure elevation and perhaps in the pathogenesis of vascular hypertrophy. Treatment with endothelin receptor antagonists may offer a novel therapy for these moderate-to-severe hypertensive patients.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveThe role of the renin–aldosterone system and the ability of renal sodium reabsorption to facilitate pressure natriuresis were analyzed by using a sufficient number of Japanese patients with essential hypertension.MethodsWe studied 3222 normal Japanese subjects (610 in Kashiwa City Hospital and 2612 in Shinshu University Hospital), 741 Japanese patients with essential hypertension (256 in Kashiwa City Hospital and 485 in Shinshu University Hospital), 20 patients with aldosterone-producing adenomas and 11 patients with idiopathic hyperaldosteronism to determine the possible roles of sodium, renal function, and plasma aldosterone concentration (PAC) on blood pressure elevation. Inappropriate elevation of aldosterone levels [elevation of the aldosterone: plasma renin activity (PRA) ratio] was used to assess aldosterone action.ResultsThe peak of the serum sodium distribution curve was approximately 2 mmol/l higher in the patients with essential hypertension than it was in controls. The prevalence of higher serum sodium concentrations (≥ 147 mmol/l) also was increased significantly hypertensive patients. Age-related deterioration of renal function did not explain the hypertension and abnormal sodium metabolism in the hypertensive patients. In stepwise regression analysis, the serum sodium concentration was related inversely to the PRA and positively to the PAC:PRA ratio. Although there was an inverse relationship between urinary sodium excretion (representing sodium intake) and the PRA, urinary sodium excretion proved not to be significant as a source of variation in the PAC or in the PAC:PRA ratio in the hypertensive patients. Although the PAC was within the normal range in patients with serum sodium concentrations of 147 mmol/l or more and an elevated PAC:PRA ratio, it was inappropriately high for the stimulus applied, as indicated by the PRA; this is similar to the situation with aldosterone-producing adenomas or idiopathic hyperaldosteronism.ConclusionSerum sodium distribution patterns differed between normal subjects and patients with essential hypertension in this Japanese population. The deterioration of renal function and increased sodium intake did not explain this abnormal sodium metabolism. A higher serum sodium concentration is related to an elevated blood pressure, and, in some patients, an inappropriate elevation of plasma aldosterone levels. Of the Japanese hypertensive patients, 10–14% exhibited serum sodium concentrations of 147 mmol/l or more and inappropriate elevations of aldosterone level (suppressed PRA and normal aldosterone level). The defect in these patients presumably lies in the inappropriately high secretion of aldosterone.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate the haemodynamic effects of insulin and their relationship to insulin resistance in essential hypertension.DesignGroup comparison between patients with essential hypertension and normal controls.SettingOutpatient clinics serving the greater Belfast area.PatientsEleven patients with essential hypertension and eight age-, sex- and weight-matched control subjects were recruited. Administration of all antihypertensive agents to the hypertensive patients was stopped 6 weeks prior to the study.MethodsLeg blood flow was measured using venous occlusion plethysmography. Insulin action was assessed using the hyperinsulinaemic euglycaemic clamp technique.ResultsThe hypertensive subjects were insulin-resistant compared with the normal controls. Insulin infusion resulted in similar increases in calf blood flow in the two groups. There was no correlation between calf blood flow and measurements of insulin sensitivity in either group.ConclusionsDifferences in whole-body glucose uptake in hypertensive and control subjects are not likely to be related to differences in insulin-induced stimulation of muscle blood flow.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs.Patients and methodsForty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose- tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 ± 7.0 mg/24 h), and as microalbuminuric when their UAE was 30–300 mg/24 h (nine patients; mean UAE 90.5 ± 86.6 mg/24 h).ResultsIn comparison with that of the normoalbuminuric group, the fasting plasma glucose concentration for the microalbuminuric group was only slightly higher (100 ± 9 versus 95 ± 8 mg/dl, NS). In contrast, the fasting insulin concentration in the microalbuminuric group was significantly higher than that observed in the normoalbuminuric group (25.2 ± 6.7 versus 16.6 ± 5.2 µU/ml,P< 0.0001). During the oral glucose-tolerance test, the area under the curve (AUC) for glucose (317 ± 41 versus 253 ± 53 mg/dl x 2/h,P< 0.001) and the AUC for insulin (253 ± 171 versus 124 ± 43 µU/ml x 2/h,P< 0.001) were significantly higher in the microalbuminuric group than were those AUC observed in the normoalbuminuric group. After adjustments for age, sex, body mass index and average 24 h ambulatory mean blood pressure were made, the fasting insulin level was associated independently with an increase in UAE in a multiple regression model with base 10 logarithm of the UAE as the dependent variable. Variations in fasting insulin level alone accounted for 33% of the UAE variance. In contrast, the 24 h ambulatory mean blood pressure, rather than the insulin level, was the strongest predictor of the left ventricular mass index.ConclusionsMild hypertensive patients with microalbuminuria were hyperinsulinemic in the absence of obesity, and their insulin level was the main determinant of microalbuminuria in these patients. Microalbuminuria in essential hypertension seems to identify patients with a cluster of cardiovascular risk factors and a bad risk profile. Thus, assessment of microalbuminuria may be useful in the stratification of risk in essential hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo compare the effects of fixed-dose preparations containing 180 mg sustained-release verapamil and 2 mg trandolapril, 100/25 mg atenolol/chlorthalidone, 20/12.5 mg lisinopril/ hydrochlorothiazide and placebo in patients with essential hypertension.DesignA 4-week placebo run-in period followed by a double-blind, placebo-controlled parallel group study lasting 8 weeks.SettingOffice practices (21 centres).PatientsPatients with essential hypertension (World Health Organization grades I or II); supine diastolic blood pressure 101–114 mmHg in week 4 of the run-in period; 215 patients were enrolled, of whom 205 were assigned randomly to double-blind therapy.Main outcome measuresReduction in supine and standing blood pressures.ResultsAll three active treatments with a single daily dose were significantly more effective than was placebo in reducing the blood pressure of seated subjects (P= 0.0001). The reductions in sitting diastolic blood pressure (DBP) from baseline to the last visit with each active treatment were comparable: 13 mmHg [95% confidence interval (CI) 16–9] with sustained- release verapamil/trandolapril, 13 mmHg (16–9) with atenolol/chlorthalidone and 12 mmHg (15–8) with lisinopril/hydrochlorothiazide. Normalization of blood pressure (DBP < 90 mmHg) was observed in 48% of patients with sustained-release verapamil/trandolapril, in 46% with atenolol/chlorthalidone and in 40% with lisinopril/hydrochlorothiazide. Response rates (normalization of DBP or a reduction in DBP by > 10 mmHg) with each active treatment were 72% for sustained-release verapamil/trandolapril, 76% for atenolol/chlorthalidone and 69% for lisinopril/ hydrochlorothiazide. All three active treatments were tolerated well.ConclusionThis study demonstrates that the low-dose combination sustained-release verapamil/trandolapril may be a suitable alternative for combinations containing a thiazide diuretic or a β-blocker for longer term management of hypertensive patients for whom combination therapy is indicated.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesTo compare the antihypertensive efficacy and tolerability of the imidazoline I1receptor agonist moxonidine, a centrally acting antihypertensive, with the angiotensin converting enzyme inhibitor enalapril.DesignAn 8-week, double-blind, randomized, placebo- controlled study involving 140 outpatients with mild-to- moderate essential hypertension.MethodsOutpatients with WHO stage I or II hypertension were enrolled in the study. After a 4-week placebo-controlled stabilization phase patients were allocated randomly to placebo, 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks. Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks. Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring.ResultsThe mean reduction in sitting blood pressure with moxonidine was similar to that with enalapril (19.5 ± 16.0/12.3 ± 8.7 versus 18.9 ± 13.7/11.8 ± 8.0 mmHg) and significantly superior to that with placebo (-4.6 ± 12.3/-4.7 ± 6.8 mmHg,P< 0.001). In addition to reducing blood pressure during conventional measurements, moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements. The trough: peak ratio for moxonidine was 0.7. Both moxonidine and enalapril were tolerated well.ConclusionsMoxonidine is an effective and well- tolerated antihypertensive, at least as good as other established forms of antihypertensive medication. The trough: peak ratio of 0.7 indicates that the drug will be effective administered once a day.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID