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Showing papers by "Robert Fagard published in 1991"


Journal ArticleDOI
TL;DR: Until the results of prospective studies on the relation between the ambulatory BP and the incidence of cardiovascular morbidity and mortality become available, the aforementioned intervals could serve as a temporary reference for clinical practice.
Abstract: To perform a meta-analysis of published reports in an attempt to determine the mean and range of normal ambulatory blood pressure (BP), 23 studies including a total of 3,476 normal subjects were reviewed. Most studies were compatible with a mean 24-hour BP in the range of 115 to 120/70 to 75 mm Hg, a mean daytime BP of 120 to 125/75 to 80 mm Hg, and a mean nighttime BP of 105 to 110/60 to 65 mm Hg. With weighting for the number of subjects included in the individual studies, the 24-hour BP averaged 118/72 mm Hg, the daytime BP 123/76 mm Hg, and the nighttime BP 106/64 mm Hg. The night/day pressure ratio averaged 0.87 for systolic and 0.83 for diastolic BP, with ranges across the individual studies from 0.79 to 0.92 and from 0.75 to 0.90, respectively. If the mean +/- 2 standard deviation interval in the various studies was considered normal, the range of normality was on average 97 to 139/57 to 87 mm Hg for the 24-hour BP, 101 to 146/61 to 91 mm Hg for the daytime BP, and 86 to 127/48 to 79 mm Hg for the nighttime BP. Until the results of prospective studies on the relation between the ambulatory BP and the incidence of cardiovascular morbidity and mortality become available, the aforementioned intervals, which summarize the experience of 23 investigators, could serve as a temporary reference for clinical practice.

207 citations


Journal ArticleDOI
TL;DR: The genetic variance of measured peak O2 uptake is significant and persists after adjustment for anthropometric characteristics, life-style factors, anaerobic energy generation, and mechanical efficiency.
Abstract: Twenty-nine pairs of monozygotic twins and 19 pairs of dizygotic twins, all male, ages 18–31 yr, performed a graded uninterrupted exercise test on the bicycle ergometer to exhaustion. By use of pat...

166 citations


Journal Article
TL;DR: In this paper, a meta-analysis suggested that hypertension may be suspected if the 24-hour blood pressure exceeds 129/87 mmHg, or if the daytime or night-time pressures are higher than 146/91 mm Hg or 127/79 mmHG, respectively, and that placebo effects are not observed when blood pressure is measured with ambulatory recorders.
Abstract: Monitoring ambulatory blood pressure, instead of taking pressure readings in hospital, avoids the so-called white-coat effect and allows more readings to be obtained over a longer period of time. It improves the accuracy of the blood pressure estimate and increases the statistical power of therapeutic trials for hypertension. Subjects with white-coat or office hypertension can be detected by ambulatory blood pressure monitoring and excluded from clinical trials. In 23 studies, including a total of 3304 normotensive subjects, the 24-h ambulatory blood pressure averaged 118/72 mmHg; the daytime and night-time pressures were 123/76 mmHg and 106/64 mmHg, respectively. If the mean plus two standard deviation (s.d.) interval is considered the upper limit of normal, the meta-analysis suggested that hypertension may be suspected if the 24-h pressure exceeds 129/87 mmHg, or if the daytime or night-time pressures are higher than 146/91 mmHg or 127/79 mmHg, respectively. On balance, most studies suggest that placebo effects on blood pressure are not observed when blood pressure is measured with ambulatory recorders. If confirmed, this observation indicates that it is possible to simplify the design of trials in the field of hypertension. Ambulatory blood pressure readings should be obtained with properly validated monitors. If the recordings are of sufficient quality, editing does not increase the precision of the subsequent statistical analyses. The statistical analyses should account for diurnal rhythms, and subject and treatment effects.

129 citations


Journal ArticleDOI
TL;DR: The Syst-Eur trial as mentioned in this paper is a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality.
Abstract: The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. This article describes the objectives and the protocol of Syst-Eur, a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups. A one-year pilot trial (1989) showed that the protocol is practicable. The Ethics Committee therefore decided to start the definite study (1990), in which randomized patients will be followed for 5 years. Recruitment of new centres and of the required 3,000 patients will last 3 years (until 1993).

103 citations


Journal ArticleDOI
TL;DR: The present population study did not confirm the hypothesis that increased exposure of the population to cadmium is associated with blood pressure elevation and with a higher prevalence of cardiovascular diseases.
Abstract: In a population study conducted from 1985 to 1989 in Belgium, the authors investigated whether exposure to cadmium is associated with blood pressure elevation and with an increased prevalence of cardiovascular diseases. The participants, aged 20-88 years, constituted a random sample of the households living in two low exposure areas (n = 803) and two high exposure areas (n = 1,283). For each exposure level, a rural and an urban district were selected. The cadmium levels in blood (8.5 vs. 11.0 nmol/liter) and urine (7.2 vs. 8.7 nmol/24 hours) were significantly (p less than 0.001) raised in the two high exposure areas compared with the two low exposure areas (p less than 0.001). Systolic pressure was similar in both rural areas, but in the urban area with high exposure systolic pressure was 5 mmHg (p less than 0.001) higher than in the control town. Diastolic pressure was similar in the four districts and the same was true for the prevalence of hypertension and of other cardiovascular diseases. Adjustment of systolic pressure for blood and urinary cadmium did not remove the difference in systolic pressure between both urban areas, suggesting that it was not related to the cadmium burden on the environment. Further analyses in individual subjects showed that neither blood pressure nor the presence of cardiovascular diseases were significantly and positively correlated with blood and urinary cadmium. Thus, the present population study did not confirm the hypothesis that increased exposure of the population to cadmium is associated with blood pressure elevation and with a higher prevalence of cardiovascular diseases.

74 citations


Journal ArticleDOI
TL;DR: In 1000 hypertensive subjects over 60 years of age, 1 year of active treatment would prevent 11 fatal cardiac events, 6 fatal and 11 non-fatal strokes and 8 cases of severe congestive heart failure.
Abstract: Hypertensive patients over the age of 60 years were admitted to a double-blind placebo-controlled trial. Patients in the actively treated group received a combined potassium-losing and -sparing diuretic (triamterene 50 mg plus hydrochlorothiazide 25 mg; n=416); this dose could be doubled and methyld

72 citations



Journal ArticleDOI
TL;DR: Exercise duration in 14 hypertensive sportsmen, aged 39 +/- 3 years and weighing 73 +/- 2 kg, was significantly decreased and atenolol induced decreases in plasma-free fatty acid concentration before and after exercise and an increase in potassium concentration after exercise, whereas enalapril and verapamil did not induce metabolic changes.
Abstract: Beta-adrenoceptor blockade can influence exercise capacity negatively, but data on the effect of converting enzyme inhibition and of calcium entry blockade on exercise capacity in hypertensive sportsmen are scarce. This report deals with the effect of the various types of antihypertensive medication on endurance exercise capacity in 14 hypertensive sportsmen, aged 39 +/- 3 years and weighing 73 +/- 2 kg (mean +/- s.e.m.). The patients were treated for 3 weeks with either placebo, atenolol (50 mg/day) enalapril (10 mg/day) or verapamil (240 mg/day) following a double-blind randomized cross-over design. At the end of each treatment period, they performed an endurance exercise test on the bicycle until exhaustion at 70% of their previously determined exercise capacity. Venous blood was sampled before and after exercise. In comparison with placebo, total exercise duration was not affected by enalapril (-3 +/- 7%) or verapamil (-7 +/- 11%). During treatment with atenolol, two patients had to interrupt their intake of the beta-blocker because of side effects. In the 12 remaining subjects, exercise duration was significantly decreased by 38 +/- 12% (P less than 0.01). Atenolol also induced decreases in plasma-free fatty acid concentration before and after exercise and an increase in potassium concentration after exercise, whereas enalapril and verapamil did not induce metabolic changes. During exercise, systolic blood pressure was decreased by atenolol (P less than 0.001) and enalapril (P less than 0.01) and diastolic blood pressure by enalapril (P less than 0.001), verapamil (P less than 0.05) and atenolol(P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

48 citations


Journal Article
TL;DR: The SHEP trail did not demonstrate a significant beneficial effect of antihypertensive treatment on any of the cardiovascular mortality endpoints, and it is possible that due to selection, the SHEP patients were not entirely representative of the elderly with ISH in the population at large.
Abstract: The Systolic Hypertension in the Elderly Program (SHEP) was a double-blind placebo-controlled outcome trial on the treatment of isolated systolic hypertension (systolic pressure: 160-219 mmHg and diastolic pressure less than 90 mmHg). From 447, 921 screenes (age greater than or equal to 60 years) 4,736 patients were randomised. A significant reduction of non-fatal stroke (37%), non-fatal myocardial infarction (33%) and left ventricular failure (54%) was observed in the active treatment group. By contrast, the reduction in transient ischaemic attacks (25%), and in total (13%), cardiovascular (20%), cerebrovascular (29%) and coronary (20%) mortality did not reach a level of statistical significance. SHEP is a landmark trial on the treatment of isolated systolic hypertension (ISH) in the elderly. However, the question to what extent the SHEP results can be extrapolated to clinical practice remains open for debate. Indeed, it is possible that due to selection, the SHEP patients were not entirely representative of the elderly with ISH in the population at large. By contrast with previous intervention studies in elderly patients with combined systolic and diastolic hypertension, the SHEP trail did not demonstrate a significant beneficial effect of antihypertensive treatment on any of the cardiovascular mortality endpoints. Confirmation or rejection of the SHEP results in other trials, including the Syst-Eur study, conducted by the rejection of the SHEP results in other trials, including the Syst-Eur study, conducted by the European Working Party on High Blood Pressure in the Elderly and the Chinese trial in elderly ISH patients, is now awaited.

38 citations


Journal Article
TL;DR: A positive relationship between systolic blood pressure and both serum total calcium and urinary copper is demonstrated in this population study.
Abstract: This report investigated the associations between blood pressure and the levels of various divalent cations in blood and urine in the population at large. The 1,982 participants (963 men and 1019 women; mean age 48 years) constituted a stratified random sample of the population of 4 Belgian districts. Systolic/diastolic pressure averaged 133/78 mmHg in men, and 128/76 mmHg in women. Serum total calcium (2.37 mmol/l), serum magnesium (1.00 mmol/l) and blood cadmium (10.0 nmol/l) were on average similar in the two sexes. By contrast, serum zinc (13.1 and 12.6 mumol/l, respectively), blood lead (0.56 and 0.36 mumol/l) and the urinary excretions of calcium (4.86 and 3.95 mmol/24h), copper (0.16 and 0.13 mumol/24h), and cadmium (9.4 and 7.2 nmol/24h) were significantly higher in men than in women. After adjustment for significant blood pressure covariates (age, body mass index, pulse rate, log gamma-glutamyltranspeptidase, smoking habits, and in women the contraceptive pill), serum total calcium was independently and positively correlated with systolic pressure in both sexes, and with diastolic pressure in women. After similar adjustments systolic pressure was positively correlated with urinary copper in men and women. In addition, systolic pressure and blood lead, and diastolic pressure and urinary cadmium were negatively correlated in men. In conclusion, this population study demonstrated a positive relationship between systolic blood pressure and both serum total calcium and urinary copper.

35 citations


Journal ArticleDOI
TL;DR: In resting conditions, a genetic component in the variability of systolic and diastolic blood pressure was found; during submaximal supine exercise only a minor genetic effect was observed; and during exercise the transmissible effect on haemodynamics and peripheral resistance was small.
Abstract: Thirty-two pairs of monozygotic and 21 pairs of dizygotic male twins aged between 18 and 31 years were studied. Blood pressure was measured and Doppler echocardiography at the level of the aorta was performed in resting conditions and at two levels of supine submaximal bicycle exercise (at a fixed w

Journal Article
TL;DR: Exercise BP is not better related to target organ damage than BP at rest in patients with essential hypertension, and exercise BP did not contribute independently fromBP at rest to their variance.
Abstract: To study whether exercise blood pressure is more closely related to the complications of hypertension than resting blood pressure, 169 patients with essential hypertension, aged 16-66 years, (WHO stages I and II), underwent a graded uninterrupted exercise test on the bicycle ergometer up to exhaustion. BP was measured in intra-arterially. Target organ damage was assessed by eye-fundus grade and by electrocardiographic voltage criteria and T-wave patterns. After adjustment for relevant covariates (age, gender, body height and weight), the manifestations of target organ damage were significantly related to systolic (r ranging from 0.19 to 0.39) and diastolic (r ranging from 0.11 to 0.30) intra-arterial pressure at supine rest. The complications of hypertension were not more closely related to BP during upright submaximal and peak exercise than to resting BP, and exercise BP did not contribute independently from BP at rest to their variance. In conclusion, exercise BP is not better related to target organ damage than BP at rest in patients with essential hypertension.

Journal ArticleDOI
TL;DR: The heritability of left ventricular structure and function was studied in 53 pairs of monozygotic and dizygotic twins by means of M-mode and Doppler echocardiography and a significant influence of heredity was detected forleft ventricular inflow and outflow characteristics.
Abstract: The heritability of left ventricular structure and function was studied in 53 pairs of monozygotic and dizygotic twins, aged 18 to 31 years, by means of M-mode and Doppler echocardiography. A significant fraction of the phenotypic variances of left ventricular wall thickness was explained by genetic variance. For the left ventricular internal dimension, however, no genetic effect was found after correction for body weight. After appropriate adjustment a genetic component of 32% was found for aortic peak flow velocity, 55% for stroke distance, and 47% for minute distance. The early and late diastolic peak flow velocities at the mitral valve showed a genetic component estimated at 43% and 26%, respectively. The inheritance of the late/early diastolic peak flow velocity ratio was estimated at 53%. In conclusion, these data suggest a significant genetic component for left ventricular structural features but not for cavity dimension. A significant influence of heredity was detected for left ventricular inflow and outflow characteristics.


Journal ArticleDOI
TL;DR: Isolated systolic hypertension (ISH) is more prevalent in elderly women than in elderly men, and there is evidence that the prevalence of ISH is decreasing.

Journal ArticleDOI
TL;DR: In human erythrocytes under acute conditions Cd2+ exerts an inhibitory effect on Na+,K(+)-ATPase enzyme in disrupted ery Throcytes and the Ca2+ stimulated K+ efflux in intact red blood cells without affecting the Na+ pump, Na+ cotransport, and Na+,Li+ countertransport activity.
Abstract: The effects of cadmium (Cd2+) on Na+,K(+)-ATPase in disrupted human erythrocyte membranes and on various transmembrane Na+ and K+ transport systems in intact erythrocyte suspensions were studied. Cadmium2+ inhibited the erythrocyte Na+,K(+)-ATPase enzyme with a 50% inhibition at a Cd2+ concentration of 6.25 microM. The Cd2+ inhibition in the human erythrocyte was non-competitive with respect to Na+,K+, and ATP. Cadmium2+ exerted no acute effect, however, on the Na+,K(+)-ATPase pump activity as measured by the ouabain sensitive 86Rb uptake or Na+ efflux in intact red blood cells. Cadmium2+ also inhibited the Ca2+ dependent K+ channels in human red blood cells, whereas it had no effect on Na+,K+ cotransport, Na+,Li+ countertransport, anion carrier, and the number of active Na+ pump units. The data indicate that in human erythrocytes under acute conditions Cd2+ exerts an inhibitory effect on Na+,K(+)-ATPase enzyme in disrupted erythrocytes and the Ca2+ stimulated K+ efflux in intact red blood cells without affecting the Na+ pump, Na+,K+ cotransport, and Na+,Li+ countertransport activity.

Journal ArticleDOI
TL;DR: The present data suggest that in subjects with a pulse rate greater than 78 beats/min a high salt intake may be associated with blood pressure elevation, whereas the opposite tendency is observed in individuals with a pulses rate less than 68 beats/Min.

Journal ArticleDOI
TL;DR: The data suggest that the capacity of increasing end-diastolic left ventricular internal dimension and increasing fractional shortening during submaximal exercise has, unlike findings at rest, a significant genetic component.
Abstract: The inheritance of cardiac changes during acute dynamic physical exercise was studied in 21 pairs of monozygotic and 12 pairs of dizygotic male twins, ages 18-31 yr. Echocardiography was performed in resting conditions and at submaximal supine bicycle exercise at a heart rate of 110 bpm. In resting conditions significant heritability could be demonstrated for end-diastolic mean wall thickness, but not for left ventricular diameter and fractional shortening. Also for the change of mean wall thickness from rest to exercise, no significant heritability could be demonstrated. The increase of end-diastolic left ventricular internal dimension from rest to exercise showed a genetic component of 24% (P less than 0.05). Inheritance accounted for 47% (P less than 0.001) of the total phenotypic variance of the increase of fractional shortening from rest to exercise. In conclusion, the data suggest that the capacity of increasing end-diastolic left ventricular internal dimension and increasing fractional shortening during submaximal exercise has, unlike findings at rest, a significant genetic component.

Journal ArticleDOI
TL;DR: It is suggested that occult cardiovascular disease does not explain the decline in cardiac output with age in patients with essential hypertension, and cardiac output was independently and inversely related to age at various levels of activity.
Abstract: It has been suggested that the decline of cardiac output with age is due to increased prevalence of disease, particularly occult coronary artery disease. Therefore, the relation of cardiac output (direct oxygen Fick method) to age was analyzed in 110 sixteen- to 64-year-old men with World Health Organization stage I or II essential hypertension at the time of the hemodynamic study, who were alive and free of cardiovascular complications 7 years later. At supine and seated rest, during upright bicycle exercise at 50 W and and at peak work load, cardiac output was inversely (p less than 0.01) related to age. These relations were independent of weight and mean intraarterial pressure. Stroke volume decreased with advancing age at supine rest, but not at rest and during exercise in the seated position. Heart rate was not affected by age in the supine position, but was slower in older patients during upright rest and at peak exercise. In conclusion, in patients with essential hypertension who remained free of cardiovascular complications for 7 years, cardiac output was independently and inversely related to age at various levels of activity. These findings suggest that occult cardiovascular disease does not explain the decline in cardiac output with age in patients with essential hypertension.

Journal ArticleDOI
TL;DR: The fall in SBP was associated with decreases in RaVL and in SV1 + RV5, after adjustment for age and changes in BMI, and was positively related to the fall in DBP after 4 years of active treatment.
Abstract: Long-term effects of antihypertensive treatment on various electrocardiogram (ECG) voltages and the association between ECG findings at randomization and subsequent mortality were evaluated in the double-blind, placebo-controlled trial of elderly hypertensive patients, conducted by the European Working Party on High Blood Pressure in the Elderly (EWPHE). Patients were treated with a combination of hydrochlorothiazide and triamterene or matching placebo; methyldopa or placebo was added if blood pressures remained high. RaVL and SV1 + RV5 at randomization were related to systolic blood pressure (SBP) and RaVL was also related to diastolic blood pressure (DBP), after adjustment for age, gender, and body mass index (BMI). When adjusted for age and body mass index, the decreases in RaVL and SV1 + RV5 were not correlated with the changes in SBP after 1 year of active treatment but the decreases in SV1 + RV5 were positively related to the fall in DBP. After 4 years of active treatment, the fall in SBP was associated with decreases in RaVL and in SV1 + RV5, after adjustment for age and changes in BMI.

Journal ArticleDOI
TL;DR: The different intervention trials in elderly hypertensives are compatible with the hypothesis that hypotensive drug treatment can decrease cardiovascular mortality mainly by decreasing cerebrovascular mortality.
Abstract: The different intervention trials in elderly hypertensives are compatible with the hypothesis that hypotensive drug treatment can decrease cardiovascular mortality mainly by decreasing cerebrovascular mortality. A decrease in the fatal and nonfatal cardiovascular event rate is mainly due to a decrease in cerebrovascular events. It is not established whether hypotensive drug treatment is advisable in symptomless patients with isolated systolic hypertension and in patients with uncomplicated hypertension above age 80. A sudden reduction in blood pressure should be avoided, but whether a progressive reduction of systolic blood pressure below 140 mmHg and of diastolic blood pressure below 85 mmHg is dangerous or advantageous remains to be established.

Journal ArticleDOI
TL;DR: The ongoing intervention studies that have been designed to examine the hypothesis that antihypertensive treatment confers a benefit to elderly patients with isolated systolic hypertension in terms of a reduced morbidity and mortality are described.
Abstract: Isolated systolic hypertension affects between 10 and 20% of the elderly population and carries a substantial risk of cardiovascular complications. As no prospective, randomized trials have produced scientific evidence of a treatment benefit in elderly patients with isolated systolic hypertension, opinion on when and how to treat this condition differs among expert committees as well as among individual doctors. This article reviews the present treatment policies in patients with isolated systolic hypertension. It describes the ongoing intervention studies that have been designed to examine the hypothesis that antihypertensive treatment confers a benefit to elderly patients with isolated systolic hypertension in terms of a reduced morbidity and mortality. The Syst-Eur trial, which was recently initiated by the European Working Party on High Blood Pressure in the Elderly, is described in greater detail.

Journal ArticleDOI
TL;DR: The relation between serum cholesterol and mortality was investigated in 822 elderly hypertensive patients randomly assigned to treatment with diuretics, with or without methyldopa, or placebo and after adjustment for gender, age, pretreatment cardiovascular complications, and systolic pressure.

Journal ArticleDOI
TL;DR: The changes in plasma renin, aldosterone, and α-atrial natriuretic peptide during xipamide administration may be related to diureticinduced volume contraction.
Abstract: The effect of xipamide on plasma α-atrial natriuretic peptide and the renin-aldosterone-kallikrein system have been studied in 12 healthy men, using a double-blind cross-over design. After a run-in period on placebo of 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of α-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained reduced. The changes in plasma α-ANP observed after 1 week of xipamide were negatively correlated with the changes in hematocrit and hemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the hematocrit and hemoglobin. The changes in plasma renin, aldosterone, and α-atrial natriuretic peptide during xipamide administration may be related to diureticinduced volume contraction.

Journal ArticleDOI
TL;DR: The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise.
Abstract: The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (p = 0.004), total (p less than 0.001), and inactive (p = 0.02) renin at rest recumbent on average by 42, 19, and 8%, respectively, and at rest sitting on average by 45, 15, and 3%, respectively. Inhibition of prostaglandins with indomethacin reduced (p less than 0.001) active and total renin at each level of work load but not (p = 0.32) inactive renin. However, the exercise-induced stimulation (p less than 0.05) of active and total renin still occur during indomethacin. Indomethacin reduced (p less than 0.001) at rest sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2 by 50 and 54%, respectively, prostaglandin F2 alpha by 36 and 39%, respectively, and 13,14-dihydro-15-keto-prostaglandin F alpha by 38 and 60%, respectively. The urinary excretion of immunoreactive prostaglandin E2 and F2 alpha was also reduced.