Abstract-This double-blind placebo-controlled study was designed to investigate the acute and sustained hormonal, renal hemodynamic, and tubular effects of concomitant ACE and neutral endopeptidase (NEP) inhibition by omapatrilat, a vasopeptidase inhibitor, in men. Thirty-two normotensive subjects were randomized to receive a placebo, omapatrilat (40 or 80 mg), or the fosinopril/hydrochlorothiazide (FOS/HCTZ; 20 and 12.5 mg, respectively) fixed combination for 1 week. Blood pressure, renal hemodynamics, urinary electrolytes and atrial natriuretic peptide excretion, and several components of the renin-angiotensin system were measured for 6 hours on days 1 and 7 of drug administration. When compared with the placebo and the FOS/HCTZ combination, omapatrilat induced a significant decrease in plasma angiotensin II levels (PϽ0.001 versus placebo; PϽ0.05 versus FOS/HCTZ) and an increase in urinary atrial natriuretic peptide excretion (PϽ0.01). These hormonal effects were associated with a significant fall in blood pressure (PϽ0.01) and a marked renal vasodilatation, but with no significant changes in glomerular filtration rate. The FOS/HCTZ markedly increased urinary sodium excretion (PϽ0.001). The acute natriuretic response to FOS/HCTZ was significantly greater than that observed with omapatrilat (PϽ0.01). Over 1 week, however, the cumulative sodium excretion induced by both doses of omapatrilat (PϽ0.01 versus placebo) was at least as great as that induced by the dose of FOS/HCTZ (PϭNS versus FOS/HCTZ). In conclusion, the results of the present study in normal subjects demonstrate that omapatrilat has favorable renal hemodynamic effects. Omapatrilat combines potent ACE inhibition with a sustained natriuresis, which explains its well-documented potent antihypertensive efficacy. Key Words: hemodynamics, renal Ⅲ sodium Ⅲ angiotensin-converting enzyme Ⅲ neutral endopeptidase Ⅲ omapatrilat Ⅲ vasopeptidase Ⅲ human A ngiotensin II is an important physiological modulator of renal function through its hemodynamic, glomerular, and tubular effects. 1 Hence, under most circumstances, interruption of the renin-angiotensin cascade with ACE inhibitors or angiotensin II type 1 receptor antagonists in humans promotes sodium excretion and increases renal blood flow without affecting glomerular filtration rate (GFR). As a result, filtration fraction decreases. 2 Atrial natriuretic peptide (ANP), the brain natriuretic peptide, and the C-type natriuretic peptide represent another family of peptides that have an important impact on renal function. 3,4 Indeed, in addition to a peripheral vasodilation, these peptides elicit diuresis and natriuresis, an attenuation of the release of renin and aldosterone and of the sympathetic nervous activity. 3 High plasma ANP and brain natriuretic peptide levels have been measured under several clinical conditions in which sodium and water retention occur, such as congestive heart failure or chronic renal failure. 3,4 In humans, the administration of exogenous ANP and the inhibition of natriuretic peptide...
The measurement of an airborne concentration in Amosite fibers above 5035 F/m 3 in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52-320 F/m 3 . The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10 −6 to 3 × 10 −5 for mesothelioma and 4 × 10 −7 to 8 × 10 −6 for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers. ER Mesothelioma Lung Cancer ER Chrysotile only K M 0.15 10 −8 Mix (Chrysotile + Amphibole) K M 1.3 10 −8 Amosite only K M 3.9 10 −8 Amphiboles (Amosite + Crocidolite) K M 7.95 10 −8
COVID-19 et médecine ambulatoire* Outils d'évaluation pour le médecin traitant dans le cadre du retour au travail des personnes vulnérables
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