摘要:

Objective:To compare the responses of angiotensin II (Ang II) and blood pressure to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme (ACE) inhibitor enalaprilSubjects:Eight non-sodium-restricted patients with mild-to-moderate essential hypertensionDesign:A single-blind crossover study. Ro 42-5892 (600 mg orally, once a day) and enalapril (20 mg orally, once a day) were given for 8 days before detailed investigations were carried out.Methods:Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions. Off-treatment and on day 8 of treatment with Ro 42-5892 and with enalapril. Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatographyResults:Plasma renin activity and Ang II were lowered by 83% [95% confidence interval (CD 61-105] and 68% (95% Cl 49-87), respectively, 0.5-1 h after Ro 42-5892, but after only 3h values had returned to baseline. Unlike this rapid and short-term suppression of Ang II, the maximal antihypertensive response to Ro 42-5892 (fall in blood pressure 12.9/9.0 mmHg) occurred only after 6h. Blood pressure returned to baseline after 8h. In response to enalapril, Ang II was maximally suppressed by 63% (95% Cl 32-94) after 2 h and by 83% (95% Cl 76-90) after 8 h. Despite early maximal Ang II suppression, the maximal antihypertensive response to enalapril occurred only after 12 h (fall in blood pressure 25.3/16.3 mmHg). With this compound a significant antihypertensive effect was still present 24 h after dosing.Conclusions:Compared with enalapril at 20 mg once a day, repeated oral administration of a single dose of Ro 42-5892 at 600 mg caused only short-term suppression of Ang II and blood pressure. Suppression of Ang II and reduction in blood pressure were temporally dissociated, both with the ACE inhibitor and the renin inhibitor. This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the circulation

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:We have shown previously that the combination of captopril and nifedipine was effective at peak response but was very short acting. We therefore decided to study the longer-acting angiotensin converting enzyme inhibitor lisinopril and the long-acting calcium antagonist amlodipine, each alone and in combination, in a double-blind, randomized crossover study in which blood pressures were measured at peak and trough. This study provided the opportunity to investigate what parameters in these patients might possibly predict the fall in blood pressure with the individual drugs and with the combinationMethods:Fifteen patients with essential hypertension (eight male, 10 Caucasian; mean age 53 years) were studied. After 1 month observation on no treatment they were entered into a single-blind run-in of placebo given once a day for 1 month. Patients were then allocated randomly to amlodipine (5 mg once a day), lisinopril (10 mg once a day) or their combination (once a day) for 1 month in a double-blind crossover study. All patients were studied on their usual diet and no dietary advice was given. Blood pressure was measured by semi-automatic ultrasound sphygmomanometer both 24 h and 6 h (trough and peak) after the last doseResults:During the crossover part of the study there was a significant additional blood pressure-lowering effect (at trough) of the combination compared with either amlodipine or lisinopril alone. Similar results were observed for the blood pressures at peak. The fall in blood pressure with lisinopril was related to baseline plasma renin activity, whereas when amlodipine was given, either alone or in combination, the fall in blood pressure was independent of baseline renin activity. The Blacks (n=5) appeared not to respond as well to lisinopril as the Caucasians (n=10). Finally, the blood pressure response to amlodipine tended to be associated with the severity of hypertensionConclusions:The results of the present study indicate that: amlodipine and lisinopril in combination have a marked additional effect on blood pressure compared with either given as a monotherapy; their potentiation of action is long-acting; Black patients tend not to respond to the monotherapy with lisinopril as well as Caucasian patients, although they respond similarly to the combination; the response to amlodipine tends to be greater the higher the initial blood pressure; and, finally, the response to lisinopril is greater the higher the plasma renin activity

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To assess the mechanisms of the blood pressure-lowering effect of a vegetarian diet in the early and later stages of dietary interventionDesign:After 2 weeks without intervention (baseline), 20 normotensive men were matched for age and body mass index and randomly allocated to an omnivorous (control) or a lacto-ovovegetarian diet for 6 weeks in a parallel trialMethods:Ambulatory blood pressures were recorded between 0800 and 1700 h on alternate days during the first week of intervention, twice in the second week and weekly thereafter. Blood samples collected after a standard breakfast were analysed for plasma noradrenaline, adrenaline, atrial natriuretic peptide (ANP), renin, aldosterone, glucose and insulin. Factor and multiple regression analyses were used to assess the association among neurohormonal factors, blood pressures and diet. Results were analysed for the first week of the diet and for the entire 6 weeksResults:Ambulatory blood pressures at work were lower on the vegetarian diet than in the controls. This blood pressure decrease was associated with a factor representing lower plasma catecholamine and renin activity levels throughout the study, and a factor representing reduced plasma glucose and insulin levels in week 1 of intervention only. Plasma ANP levels were significantly higher during week 1 of the vegetarian dietConclusions:A blood pressure lowering effect of a vegetarian diet during normal working activity was shown. Using factors derived from the biochemical variables, results were in keeping with the hypothesis that these effects may be mediated by reduced sympatho-adrenal activity consequent to altered glucose and insulin handling. An early increase in plasma ANP may contribute to the blood pressure reduction

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:Salt sensitivity and the magnitude of systolic blood pressure have been linked to haptoglobin (Hp) polymorphism in normotensives. The aim of the present study was to investigate the indices of hypertension, the severity of complications and the occurrence of coronary and peripheral artery disease for the various haptoglobin phenotypes and their relation to the therapeutic needs (number and class of drugs) of established arterial hypertensivesDesign:Haptoglobin polymorphism was studied in 302 Caucasians with established essential arterial hypertension who had been treated for at least 1 yearMethods:Haptoglobin polymorphism was studied using starch-gel electrophoresis of haemoglobin-supplemented serumResults:The relative allele frequencies of Hp 1 and Hp2 (0.360 and 0.640, respectively) in established hypertensives were comparable with those of the control population. Logistic regression analysis confirmed that Hp2-2 contributes to the therapeutic needs in hypertension. The most important factors determining therapeutic needs were coronary artery disease, Hp2-2 phenotype, body mass index (BMI) and left ventricular hypertrophy. Although no contributive effect of serum haptoglobin concentration could be derived from the logistic regression approach, analysis of serum haptoglobin concentration demonstrated a concentration-related effect on therapeutic needs for the Hp2-2 phenotype onlyConclusions:The present study suggests that hypertensives with an Hp 2-2 phenotype need more complex combinations of antihypertensive drugs to reduce blood pressure to the same level. The hypertensive patient carrying Hp 2-2 is more likely to accumulate atherosclerotic lesions of the coronary or peripheral arteries, despite comparable lipid levels, smoking habits and BMI. Hp1-1 patients are characterized by a younger age at diagnosis and a lower complication rate. In view of the greater therapeutic needs and the higher complication rate, Hp2-2 hypertensives need more careful follow-up

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Objective:To establish the profiles of 24-h non-invasive ambulatory blood pressure measurement (ABPM) during the trimesters of pregnancy and the puerperium in normotensive healthy primigravidaeDesign:A prospective study in which 24-h ABPM was performed on five occasions in each subject: in the first trimester between 9 and 16 weeks' gestation; in the second trimester between 18 and 24 weeks; in the third trimester between 26 and 32 weeks and between 33 and 40 weeks; and finally at 6 weekspost partumMethod:One hundred and six Caucasian primigravid women who were normotensive at their first booking visit were recruited consecutively from the antenatal clinic and had 24-h ABPM performed with the SpaceLabs 90207 ambulatory systemResults:Of the 106 women recruited, 98 completed 24-h ABPM on four of the five measurement occasions. Four women delivered prematurely before 33 weeks' gestation, thereby missing one ABPM measurement. Changes during pregnancy and the puerperium were assessed against the ABPM performed in the first trimester. There was no difference for daytime or night-time systolic blood pressure between 9 and 33 weeks, but it rose significantly from 33 to 40 weeks. At 6 weekspost partum, systolic blood pressure was not significantly different from the daytime pressure in the first-trimester ABPM but was raised significantly at night. Diastolic blood pressure decreased significantly between 18 and 24 weeks for both daytime and night-time. From 33 to 40 weeks it increased in parallel with systolic blood pressure, and at 6 weeks post partum it was raised significantly compared with first-trimester values for daytime and night-time. The nocturnal fall in blood pressure was preserved throughout pregnancy with a significant difference between daytime and night-time measurements present on all measurement occasions for systolic, diastolic and mean blood pressures and heart rate. There were significant differences between daytime ABPM and clinic blood pressure for both systolic and diastolic blood pressure up to 33 weeks. From 33 weeks until 6 weeks post partum there was no significant difference between daytime ambulatory and clinic blood pressuresConclusion:This study provides reference values for ABPM in healthy primigravidae with generally uncomplicated pregnancies

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Introduction:This document is the result of discussions held during a Scientific Workshop in Brescia, Italy, where the numerous methods, old and new, for evaluation of organ damage in hypertension were considered. Not all of the methods can be recommended as routine diagnostic procedures for every hypertensive subject. Current routine diagnosis of organ damage by clinic blood pressure, retinal appearances, the electrocardiogram, serum creatinine estimation and urinary analysis will probably suffice; of the more refined methods, only the echocardiogram is likely to be often included in the examination of hypertensive patients. All of the other techniques will be useful in the diagnostic approach to patients with particular problems, or for the purposes of special investigationRecommendations:It is recommended that the validity of the methods, the clinical relevance of the abnormalities (including left ventricular hypertrophy, reduced coronary reserve, arterial changes in the eye grounds, reduced large artery compliance and microalbuminuria) and the potential benefits of therapeutically reverting these alterations should be assessed by including organ damage evaluation in future epidemiological and interventional trials in hypertension

ISSN:0263-6352    

出版商:OVID    

年代:1993

数据来源: OVID