Showing papers by "Robert Fagard published in 1982"

Increase in plasma aldosterone during prolonged captopril treatment.

Abstract: Plasma aldosterone concentration was measured in seven patients before and during long-term angiotensin II suppression with captopril. Plasma aldosterone decreased initially from 62 to 9 pg/ml (p

Influence of anti-hypertensive therapy on serum cholesterol in elderly hypertensive patients. Results of trial by the European Working Party on High blood pressure in the Elderly (EWPHE).

Abstract: In the European Working Party trial on High blood pressure in the Elderly, patients over 60 are randomly allocated either to receive diuretic capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene or matching placebos. If the blood pressure remains high those receiving active diuretic treatment also receive methyldopa. Those receiving a placebo diuretic area given placebo methyldopa tablets. The study is double blind, started in 1974 and is still in progress. Three hundred and thirty-one patients have now been followed for 1 year and of these 190 have been followed for 2 and 90 for 3 years. After 1 year the serum cholesterol in the placebo group fell by an average of 10.4 mg/100 ml; over 2 years the fall was 16.0 mg/100 ml and over 3 years 20.8 mg/100 ml (6.7%). The corresponding results for the actively treated group were falls of 3.1 mg/100 ml; 20.3 mg/100 ml and 17.3 mg/100 ml (6.6%). Over a period of up to 3 years the average fall in cholesterol was 5.9 mg/100 ml/year in the placebo group and 5.0 mg/100 ml/year in the actively treated group. Thus the changes in serum cholesterol were similar whether the patients received active or placebo medication. In particular there was no evidence for an increase in cholesterol nor for a smaller decrease during diuretic therapy. In the actively treated group the fall in blood pressure in the more hypertensive patients was accompanied by a fall both in haematocrit and serum cholesterol. In patients with less severe hypertension, active treatment was not accompanied by a fall in either hematocrit or cholesterol. These different responses of serum cholesterol in the more and less severe hypertensives in the present study could explain some of the previous conflicting reports on the influence of diuretic treatment on serum cholesterol.

Response of the systemic and pulmonary circulation to converting-enzyme inhibition (captopril) at rest and during exercise in hypertensive patients.

Abstract: Twenty sodium-replete patients with hypertension were allocated either to a placebo or to a captopril treatment group. Each patient was investigated in rest-recumbent (RR) and rest-sitting (RS) positions and during an uninterrupted, graded, submaximal exercise test (up to the anaerobic threshold) before treatment, and with a similar protocol 75 minutes after treatment with captopril or placebo on the same morning. Captopril decreased brachial intraarterial pressure by 7/4 mm Hg at RR, by 16/10 mm Hg at RS, and by 19/10 mm Hg during exercise (p less than 0.001), based on a decrease of systemic vascular resistance (p less than 0.001). Slight increases of cardiac output and of heart rate were noted at rest; cardiac output was not significantly affected during exercise, but the increase of heart rate of 2.4 beats/min was significant (p less than 0.01). Captopril decreased pulmonary artery (p less than 0.05) and capillary wedge pressures (p less than 0.001), with unchanged pulmonary vascular resistance. The data indicate that the action of captopril is characterized by arteriolar and possibly venous dilatation both at rest and during exercise. Pulmonary vascular resistance, however, is not affected.

Influence of beta adrenergic blockade on effects of physical training in patients with ischaemic heart disease.

Abstract: Reduction in heart rate during submaximal exercise is often used to judge the progress of patients with ischaemic heart disease in the course of a physical training programme. Some patients, however, are treated with beta adrenergic blocking drugs and it remains controversial if chronic beta blockade influences the effects of training and if heart rate remains a useful guide in the evaluation of the state of training of these patients. Male postinfarction patients, 15 treated with and 15 without beta blockers, were trained for three months, three times a week. Cardiorespiratory results from uninterrupted incremental exercise tests before and after training were compared. In each subgroup, the heart rate and systolic blood pressure were significantly reduced. For heart rate the decrease after training became more pronounced with increasing work load and the overall reduction was significantly less in the beta blocker group compared with the patients not treated with beta blockers. For systolic blood pressure the training-induced reductions were more pronounced in the patients on beta blockers. The increase of peak oxygen uptake was similar in the patients with and without beta blockers, namely 36% and 34.5%. At submaximal exercise carbon dioxide output, pulmonary minute ventilation, and the respiratory exchange ratio were lower after training, and these effects of training were similar whether or not the patients were on beta blockers. The study shows that the usual effects of training are observed in patients on beta blockers, and that heart rate remains a useful guide to their evaluation throughout a physical training programme.

Hemodynamic response to converting enzyme inhibition at rest and exercise in humans.

Abstract: The response of the systemic circulation to acute inhibition of the converting enzyme with 25 mg of oral Captopril (Squibb) was studied in six normal sodium-replete male volunteers at rest and during exercise, together with its effects on exercise capacity for graded uninterrupted exercise. In recumbent subjects at rest Captopril did not affect arterial pressure or heart rate, and plasma renin activity rose 2.5-fold (P less than 0.05). In subjects in the sitting position, at rest and during exercise until exhaustion, Captopril reduced mean brachial intra-arterial pressure by an average of 7 Torr in comparison to placebo (P less than 0.001). Captopril9s hypotensive effect was caused by a reduction of systemic vascular resistance (P less than 0.01), without changes of cardiac output (measured by CO2 rebreathing), heart rate, or stroke volume. Plasma renin activity was significantly higher during Captopril (P less than 0.001). Peak oxygen uptake and exercise duration were the same after administration of Captopril or placebo. The data demonstrate that the renin-angiotensin system is not involved in the homeostasis of blood pressure in supine sodium-replete humans, but has a modest role in blood pressure regulation when posture is changed from supine to upright. The orthostatic effect of Captopril is maintained during upright exercise. Furthermore the reduction of systemic vascular resistance by Captopril does not affect peak oxygen uptake.

Antihypertensive therapy in patients above age 60 with systolic hypertension. A progress report of the European Working Party on High Blood Pressure in the Elderly (EWPHE).

Abstract: 1. Although systolic blood pressure elevation is responsible for increased incidence of cardiovascular accidents in old people, the preventive benefit of lowering systolic hypertension in elderly has not been confirmed. 2. A double blind study comparing the effects of a placebo and of an active regimen (hydrochlorothiazide-triamterene with or without methyldopa) in people over 60 years with isolated systolic hypertension has been undertaken by the European Working Party on High blood pressure in the Elderly (EWPHE). 3. The actively treated group shows a lowered sitting blood pressure (-15/6 mm Hg), a mild increase of serum creatine, serum uric acid and blood glucose and a mild decrease of serum potassium after two years of treatment when compared to the spontaneous changes observed in the placebo treated group. 4. The study is continuing to evaluate if the blood pressure reduction prevents or reduces the incidence of cardiovascular accidents, although some biochemical changes were provoked by the treatment.

Hemodynamic response to captopril at rest and during exercise in hypertensive patients

Abstract: Captopril in 20 hypertensive patients acutely reduced brachial intraarterial pressure at rest and during exercise, based on a reduction in systemic vascular resistance. Heart rate increased slightly whereas stroke volume was not affected. Plasma angiotensin II was significantly reduced whereas plasma renin activity increased.

Response of the systemic pulmonary circulation to labetalol at rest and during exercise

Abstract: 1 Labetalol was administered to 18 hypertensive patients for an average duration of 2.44 weeks, with an average final daily dose of 1.65 g (principally to study its short-term haemodynamic effects). 2 Labetalol decreased resting heart rate by 16% and maximal exercise heart rate by 21%; the phenylephrine-induced increase in systolic brachial arterial pressure was reduced by 36%. 3 During labetalol treatment brachial arterial pressure was decreased by 29/15 mmHg in the recumbent position, by 41/23 mmHg at rest sitting and by 53/23 mmHg at maximal exercise; total peripheral resistance was not significantly affected at rest recumbent but was reduced at sitting and at exercise; cardiac output was decreased in all conditions. 4 Labetalol reduced mean pulmonary arterial and capillary wedge pressures only in the sitting position. Pulmonary vascular resistance remained unchanged. 5 The drug produced significant decreases in plasma renin activity and in plasma aldosterone concentration.

Captopril in the treatment of hypertension

Abstract: SummaryAngiotensin-I-converting enzyme is responsible for the conversion of angiotensin I to the potent vasopressor angiotensin II and for degrading the vasodepressor bradykinin. Several converting-enzyme inhibitors have been synthesized of which captopril has been most widely used in human hypertension. This review deals with its pharmacology, haemodynamic effects, mechanisms of action, clinical usefulness and side-effects. It is concluded that converting-enzyme inhibitors are a new and interesting group of antihypertensive agents. However, the toxicity of the first molecule, captopril, remains a serious problem: prescription of this drug should be limited to specific forms of hypertension.

Antihypertensive therapy in patients above age 60 years. Eighth Interim Report of the European Working Party on High Blood Pressure in the Elderly (EWPHE)

Abstract: SummarySeven hundred and ninety-two hypertensive patients above the age of 60 years have entered the double-blind multicentre trial of the European Working Party on High Blood Pressure in the Elderly (EWPHE). Half were treated with I capsule daily containing 2.5 mg hydrochlorothiazide and 50 mg triamterene and half were given placebo. If blood pressure control was not adequate in those receiving active treatment, a second capsule was given and, if necessary, up to 2 g methyl-dopa/day. No significant differences between the groups were present prior to randomization. A significant blood pressure difference of 20/8 mmHg was obtained between the groups and maintained during 5 years of follow-up. No major disturbances in serum potassium or serum sodium were noted. On the other hand. during the initial phase an increase in serum creatinine and serum uric acid was noted in the actively-treated group which was maintained during the later years. This increase in serum creatinine was related to the decrease in sit...

Hypertension in Elderly

Abstract: Blood pressure increases with age in most people. Being more marked for systolic pressure, this increase leads to an increase in pressure amplitude. This is illustrated by Figure 1 which shows the systolic and diastolic blood pressures of a representative sample of a Belgian village [1]. There is no certainty, however, that this phenomenon continues at an extremely advanced age. Cross-sectional studies are contradictory in this respect. In the 1753 subjects over 60 years old in Edwards’ study [2] the systolic pressure shows a quasilinear rise up to the age of 70 and then starts to decrease, while diastolic blood pressure remains stable after the age of 60. In Masters’ study as well, systolic and diastolic blood pressure in 5757 subjects over 65 years old decreased in women and became stabilized in men after the age of 75 years [3].

Plasma prostaglandins, renin, and catecholamines at rest and during exercise in hypertensive humans

Abstract: Plasma prostaglandins (PGE and PGF alpha), catecholamine concentration, and plasma renin activity (PRA) were measured during an uninterrupted graded exercise test on the bicycle ergometer in 11 hypertensive patients. Blood was withdrawn from the brachial and pulmonary arteries after 30 min of recumbent rest, after 15 min of rest sitting, and at the final work load of the exercise test, which averaged 143 +/- 16.5 W. Exercise did not provoke a significant change in these plasma PGE or PGF alpha concentrations, whereas a rise (P less than 0.001) in arterial PRA and (nor)epinephrine concentration was observed. It is thus unlikely that PGE or PGF alpha is an important determinant of PRA release during exercise, although circulating levels of PGE and PGF alpha do not necessarily reflect release rate or activity in the kidney.

Anaerobic threshold for long-term exercise and maximal exercise performance.

Abstract: The thyroid proteins and iodocompounds were analysed in the thyroid tissue of 4 patients with nontoxic goitre. Subtotal thyroidectomy was performed for tracheal compression. The thyroid components were labelled with a trace amount of 125I before operation. One patient had congenital goitre and hypothyroidism with cretinoid features. Three other patients belonged to the same family. Two had congenital goitre, one of them with subclinical and biochemical hypothyroidism. There was a range of thyroglobulin (TG) deficiency ranging from virtual absence of TG in the most affected patient to 17% of normal in the least affected one. There seemed to be an inverse relationship between TG content and clinical signs. Also with decreasing TG more iodocompounds were found in the 3-8 S region on gradient centrifugation. In the most affected patient all the radioactivity was in the 3-8 S region, in the least affected one it was all found in the 19 S and 27 S regions. The other patients had an intermediate pattern. The 3-8 S fraction contained albumin, IgG and some material which reacted like TG on immunoelectrophoresis except for the least affected patient. The iodine content was normal whereas the iodination of TG was low-normal or low. Iodotyrosines and iodothyronines were found in all glands analysed on column chromatography but only in the most heavily affected patient did the ratio iodotyrosines/iodothyronines seem to be elevated. Evidently TG was not necessary for hormone formation in this gland but the efficiency of the matrix seemed not to suffice for normal hormone production.

The relative effect of mental and physical activity on blood-pressure and heart rate during the waking-up process

Abstract: 1 The morning rise in blood pressure and heart rate was studied in 18 patients with mild blood pressure elevation Passing from sleep to the drowsy state raised blood pressure and heart rate very little while the awake state (reading a newspaper sitting in bed) increased the mean blood pressure by 132 mm Hg and the heart rate by 57 beats per minute 2 Subsequent application of mental stress (arithmetic) in one third of the patients or physical activity in the upright position in another third showed a different pattern of response Mental stress mainly raised the blood pressure while physical activity in the upright position mainly raised the heart rate

Fluctuations in the plasma angiotensin I converting enzyme activity during long-term treatment with captopril.

Abstract: Eight hypertensive patients on chronic captopril treatment were studied: blood pressure, plasma converting enzyme activity (pCEA) and various components of plasma renin-angiotensin-aldosterone system were measured repeatedly, immediately before and up to 7 hours after the usual morning dose of captopril in 5 patients, or a matching placebo in 3 patients. In the patients, receiving a placebo no significant changes were observed over a 7 hour period in pCEA, plasma renin activity (PRA), plasma angiotensin II (ANG II) plasma aldosterone (PAC) and blood pressure. In patients receive captopril (200 mg) pCEA rapidly decreased, reaching after 2 hours a minimum, corresponding to nearly 20 per cent of its reference value. Thereafter pCEA increased and after 7 hours remained only slightly depressed. Within the first hour after captopril intake a small but significant decrease of ANG II and PAC was observed, while PRA and blood pressure remained unchanged throughout the study period. A continuous low pCEA level is therefore not necessary to achieve a sustained blood pressure lowering effect during chronic captopril treatment.

Biological Significance of Active and Inactive Renin in Hypertensive Patients

Abstract: The significance of active and inactive renin was investigated by comparison of an in vitro assay of active, total and inactive plasma renin concentration (APRC, TPRC, IPRC) and plasma angiotensin II concentration (PA II) with an in vivo change in mean arterial pressure (MAP) produced by angiotensin antagonism with saralasin and by angiotensin converting enzyme blockade with captopril. A significant relationship between the changes in MAP during saralasin and captopril with the pre-treatment level of APRC, TPRC and PA II were found; while the pre-existing level of inactive renin was not a predictor for the hypotensive effect of saralasin and captopril. During captopril and saralasin significant increases in TPRC and APRC were found and no change in IPRC.