Titre du document / Document title

Persistent effects on blood pressure and renal function of perindopril alone or combined with losartan in lyon hypertensive rats

Auteur(s) / Author(s)

NAELTEN Gaëlle ⁽¹⁾ ; LIU Kiao-Ling ⁽¹⁾ ; CHAPUIS Bruno ⁽¹⁾ ; MING LO ⁽¹⁾ ;

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

⁽¹⁾ Département de Physiologie et Pharmacologie Clinique, Faculty de Pharmacie, Université Claude Bernard Lyon 1, Lyon, FRANCE

Résumé / Abstract

Background: In Lyon genetically hypertensive (LH) rats, an early and long-term angiotensin-converting enzyme (ACE) inhibition with perindopril prevents their hypertension and renal alterations. The present work aimed to determine whether: 1) these effects persist after treatment withdrawal; 2) a short-term additional angiotensin II type 1 (AT1) receptor blockade with losartan potentiates these effects; and 3) an early combination of low doses of perindopril and losartan produces the same prolonged effects as monotherapy with a higher dose of perindopril. Methods: Perindopril (0.4 or 3 mg/kg/day orally) was given from 3 to 12 weeks of age to male LH rats. In other perindopril-treated LH rats, losartan (10 mg/kg/day orally) was added 1 week before perindopril withdrawal and during a 3-week period. In another group of LH rats, perindopril (0.1 mg/kg/day) and losartan (2.5 mg/kg/day) were given together from 3 to 12 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored using radio-telemetry and renal function studied in anesthetized rats. Results: Eight weeks after perindopril withdrawal, a significant reduction (P <.05) in SBP and DBP was observed with the both doses (SBP: 135 ± 3, 139 ± 5 v 157 ± 4; DBP: 89 ± 4, 93 ± 5 v 111 ± 3 mm Hg for 0.4 and 3 mg/kg/day v untreated LH rats). This was accompanied by a persistent decrease in urinary protein excretion and a long-lasting improvement in pressure natriuresis. The persistent antihypertensive effect was not improved by short-term addition of losartan. Interestingly, the early combination of perindopril with losartan at fourfold lower doses produced similar persistent antihypertensive and renoprotective effects. Conclusions: The blood pressure reduction produced by an early ACE inhibition in LH rats persists long after treatment withdrawal and is associated with an improvement in renal function. The combination of low doses of perindopril and losartan reveals a long-term effect similar to that of a monotherapy with a higher dose of perindopril.

Revue / Journal Title

American journal of hypertension   ISSN 0895-7061 

Source / Source

2005, vol. 18 (1), n^o5, pp. 699-706 [8 page(s) (article)] (31 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, New York, NY, ETATS-UNIS  (1988) (Revue)

Mots-clés anglais / English Keywords

Octapeptide ; Peptide hormone ; Tetrazole derivatives ; AT1 angiotensin receptor ; Non peptide compound ; Biphenyl derivatives ; Enzyme ; Hydrolases ; Peptidases ; Peptidyl-dipeptidases ; Peptidyl-dipeptidase A ; Enzyme inhibitor ; Vertebrata ; Mammalia ; Rodentia ; Antihypertensive agent ; Angiotensin antagonist ; Angiotensin II ; ACE inhibitor ; Rat ; Animal ; Losartan ; Perindopril ; Renal function ; Blood pressure ; Arterial pressure ; Hypertension ; Cardiovascular disease ;

Mots-clés français / French Keywords

Octapeptide ; Hormone peptide ; Tétrazole dérivé ; Récepteur angiotensine AT1 ; Composé non peptide ; Biphényle dérivé ; Enzyme ; Hydrolases ; Peptidases ; Peptidyl-dipeptidases ; Peptidyl-dipeptidase A ; Inhibiteur enzyme ; Vertebrata ; Mammalia ; Rodentia ; Antihypertenseur ; Antagoniste angiotensine ; Angiotensine II ; Inhibiteur angiotensin converting enzyme ; Rat ; Animal ; Losartan ; Périndopril ; Fonction rénale ; Pression sanguine ; Pression artérielle ; Hypertension artérielle ; Appareil circulatoire pathologie ;

Mots-clés espagnols / Spanish Keywords

Octapéptido ; Hormona péptido ; Tetrazol derivado ; Receptor angiotensina AT1 ; Compuesto no péptido ; Bifenilo derivado ; Enzima ; Hydrolases ; Peptidases ; Peptidyl-dipeptidases ; Peptidyl-dipeptidase A ; Inhibidor enzima ; Vertebrata ; Mammalia ; Rodentia ; Antihipertensivo ; Antagonista angiotensina ; Angiotensina II ; Inhibidor angiotensin converting enzyme ; Rata ; Animal ; Losartán ; Perindopril ; Función renal ; Presión sanguínea ; Presión arterial ; Hipertensión arterial ; Aparato circulatorio patología ;

Mots-clés d'auteur / Author Keywords

Hypertension ; renal function ; angiotensin- converting enzyme inhibitor ; angiotensin II type 1 receptor antagonist ;

Localisation / Location

INIST-CNRS, Cote INIST : 21579, 35400012454956.0180