Titre du document / Document title

Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans

Auteur(s) / Author(s)

AZIZI M. ⁽¹⁾ ; EZAN E. ⁽²⁾ ; RENY J.-L. ⁽¹⁾ ; WDZIECZAK-BAKALA J. ⁽³⁾ ; GERINEAU V. ⁽³⁾ ; MENARD J. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Centre d'Investigations Cliniques, Hôpital Broussais, INSERM et Assistance Publique des Hôpitaux de Paris, FRANCE
⁽²⁾ CEA, Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette, FRANCE
⁽³⁾ Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, FRANCE

Résumé / Abstract

We investigated the contributions of angiotensin-converting enzyme (ACE) and glomerular filtration to creating the new metabolic balance of the hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute and chronic ACE inhibition in healthy subjects. We also studied the effect of chronic renal failure on the plasma concentration of AcSDKP during long-term ACE inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8-fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE activity over time showed an intermittent reactivation of ACE between each captopril dose. In subjects with chronic renal failure (creatinine clearance<60 mL/min per 1.73 m²), plasma AcSDKP levels were 22 times higher (95% confidence interval, 15 to 33) in the ACEI group (n=35) than the control group (n=23); in subjects with normal renal function, they were only 4.1 times higher (95% confidence interval, 3.2 to 5.3) in the ACEI group (n=19) than the non-ACEI group (n=21). Renal failure itself led to a slight increase in plasma AcSDKP concentration. In conclusion, intermittent reactivation of ACE between doses of an ACEI is the major mechanism accounting for the lack of major AcSDKP accumulation during chronic ACE inhibition in subjects with normal renal function.

Revue / Journal Title

Hypertension   ISSN 0194-911X   CODEN HPRTDN 

Source / Source

1999, vol. 33, n^o3, pp. 879-886 (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott, Hagerstown, MD, ETATS-UNIS  (1979) (Revue)

Mots-clés anglais / English Keywords

Captopril ; ACE inhibitor ; Renal failure ; Chronic ; Metabolism ; Single dose ; Treatment ; Chemotherapy ; Comparative study ; Human ; Oral administration ; Multiple dose ; Urinary system disease ; Kidney disease ;

Mots-clés français / French Keywords

Captopril ; Inhibiteur angiotensin converting enzyme ; Insuffisance rénale ; Chronique ; Métabolisme ; Dose unique ; Traitement ; Chimiothérapie ; Etude comparative ; Homme ; Voie orale ; Dose répétée ; Peptide AcSDKP ; Appareil urinaire pathologie ; Rein pathologie ;

Mots-clés espagnols / Spanish Keywords

Captopril ; Inhibidor angiotensin converting enzyme ; Insuficiencia renal ; Crónico ; Metabolismo ; Dosis única ; Tratamiento ; Quimioterapia ; Estudio comparativo ; Hombre ; Vía oral ; Dosis múltiple ; Aparato urinario patología ; Riñón patología ;

Localisation / Location

INIST-CNRS, Cote INIST : 18059, 35400007401749.0190