Plasma Angiotensins, Renin, and Blood Pressure During Acute Renin Inhibition by CGP 38 560A in Hypertensive Patients

The new renin inhibitor CGP 38560A has been shown to block angiotensin (ANG) production in healthy volunteers. In order to determine its potential antihypertensive effect, the compound was administered in a 30-min infusion, in 12 hypertensive patients (mean blood pressure (BP): 112.8 ± 3.5 mm Hg). These patients were selected for their sensitivity to Captopril: a single oral dose of 50 mg Captopril lowered their mean BP by 8.8 ± 2.2 mm Hg after 30 min and by 15.3 ± 1.5 mm Hg after 90 min. At the end of the renin inhibitor infusion, mean blood pressure decreased by 5.7 ± 2.2 mm Hg in the six patients infused with the dose of 0.125 mg/kg and by 6.0 ± 1.8 mm Hg in the six patients infused with 0.250 mg/kg. The fall in blood pressure was correlated to the initial plasma renin activity (PRA) (r = 0.61, P < .05). A dose-dependent effect was observed on plasma ANG I which fell by 74% with 0.125 mg/kg and by 94% with 0.250 mg/kg. Identical falls were found for plasma ANG II (72% and 94%, respectively) and ANG I and ANG II were well correlated (r = 0.91, P < .001). The fall in BP was correlated to the fall in plasma ANG I (r = 0.77, P < .01). The time-course of the BP changes was parallel to the changes in plasma angiotensins, as were the slightly delayed rise and fall in active renin measured by a direct immunoradiometric assay. When measured by the conventional ANG I radioimmunoassay, PRA values indicated a long-lasting inhibition. The arte- factual nature of the latter result is demonstrated by the different results obtained with an ANG I antibody-trapping radioimmunoassay, which followed more closely plasma ANG I levels. Am J Hypertens 1989; 2:819-82

Plasma angiotensins, renin, and blood pressure during acute renin inhibition by CGP 38 560A in hypertensive patients.

The new renin inhibitor CGP 38560A has been shown to block angiotensin (ANG) production in healthy volunteers. In order to determine its potential antihypertensive effect, the compound was administered in a 30-min infusion, in 12 hypertensive patients (mean blood pressure (BP): 112.8 +/- 3.5 mm Hg). These patients were selected for their sensitivity to captopril: a single oral dose of 50 mg captopril lowered their mean BP by 8.8 +/- 2.2 mm Hg after 30 min and by 15.3 +/- 1.5 mm Hg after 90 min. At the end of the renin inhibitor infusion, mean blood pressure decreased by 5.7 +/- 2.2 mm Hg in the six patients infused with the dose of 0.125 mg/kg and by 6.0 +/- 1.8 mm Hg in the six patients infused with 0.250 mg/kg. The fall in blood pressure was correlated to the initial plasma renin activity (PRA) (r = 0.61, P less than .05). A dose-dependent effect was observed on plasma ANG I which fell by 74% with 0.125 mg/kg and by 94% with 0.250 mg/kg. Identical falls were found for plasma ANG II (72% and 94%, respectively) and ANG I and ANG II were well correlated (r = 0.91, P less than .001). The fall in BP was correlated to the fall in plasma ANG I (r = 0.77, P less than .01). The time-course of the BP changes was parallel to the changes in plasma angiotensins, as were the slightly delayed rise and fall in active renin measured by a direct immunoradiometric assay. When measured by the conventional ANG I radioimmunoassay, PRA values indicated a long-lasting inhibition.(ABSTRACT TRUNCATED AT 250 WORDS

Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype

À propos de la notion de marché et de prix du médicament (commentaire)

Jeunemaitre Alain. À propos de la notion de marché et de prix du médicament (commentaire). In: Sciences sociales et santé. Volume 8, n°1, 1990. pp. 73-81

Décomposition, recomposition des souverainetés : les politiques de concurrence en Europe

Depuis 1945, deux effets parallèles ont entraîné une recomposition de la souveraineté dans le domaine des politiques de concurrence. Le premier a vu un retrait de la sphère proprement politique au profit de l'organisation d'un débat public technique, fondé sur le droit et l'économie. Des institutions indépendantes, au carrefour de l'administration et de la justice, ont reçu mission de traiter les problèmes posés par certains comportements ou certaines structures de marché. La souveraineté s'est trouvée morcelée entre le politique, pas complètement absent, et ces institutions qui, au fil du temps, ont affirmé leur légitimité. Parallèlement, les autorités communautaires, Commission et Cour Européenne de Justice, ont affirmé leur pouvoir en matière de politique de concurrence. Les pouvoirs publics nationaux se sont trouvés contraints par les décisions de Bruxelles, et dessaisis en partie des dossiers les plus importants. La souveraineté s'est déplacée au niveau transnational. L'éclairage donné conduit à s'interroger sur les évolutions futures : le processus de décomposition/recomposition de la souveraineté n'est en effet pas achevé.Dumez Hervé, Jeunemaître Alain. Décomposition, recomposition des souverainetés : les politiques de concurrence en Europe. In: Politiques et management public, vol. 9, n° 3, 1991. La souveraintenté éclatée : les nouveaux cadres de l'action publique - Actes du Quatrième Colloque International Bruxelles - 1 1/12 octobre 1990 - (Deuxième partie) - Mutation des espaces : marché, logiques locales, négociation sociale. pp. 51-62

Gènes et pression artérielle

Équipe 1 – responsable : Xavier Jeunemaitre Thème 1: Identification de gènes et de variants impliqués dans la régulation du métabolisme hydrosodé, l’hypertension artérielle et ses conséquences vasculaires G. Beaurain, X. Jeunemaitre, H. Louis-dit-Picard, J. Perdu, P.F. Plouin, R. Vargas-Poussou, X. Zhou. L’objectif de notre projet est d’identifier de nouveaux gènes ou de nouveaux variants qui influencent de façon significative le métabolisme hydrosodé, l’hypertension artérielle (HTA) ou des p..

Gènes et pression artérielle minéralocorticoïde

Équipe 1 - Responsable : Xavier Jeunemaitre Thème 1 : Identification de gènes et de variants impliqués dans la régulation du métabolisme hydrosodé, l’hypertension artérielle et ses conséquences vasculaires Membres : Geneviève Beaurain, Anne-Laure Fauret, Julie Faugeroux, Xavier Jeunemaitre, Pierre-François Plouin, Rosa Vargas-Poussou L’objectif de notre projet est d’identifier de nouveaux gènes ou de nouveaux variants qui influencent de façon significative le métabolisme hydrosodé, l’hyperten..