Vasopeptidase inhibition prevents target organ damage and improves survival in spontaneously hypertensive rats.
J Renin Angiotensin Aldosterone Syst
; 7(3): 155-61, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-17094052
ABSTRACT
BACKGROUND:
Vasopeptidase inhibition has been shown to be an effective antihypertensive principle but its long-term effects on hypertensive target organ damage are not known. We investigated the myocardial, vascular and renal effects of chronic vasopeptidase inhibition in arterial hypertension. METHODS ANDRESULTS:
One hundred and thirty-nine male spontaneously hypertensive rats aged 15 months were treated chronically with either the pure angiotensin-converting enzyme (ACE) inhibitor, ramipril (1 mg/kg/d in drinking water, n=46), or the vasopeptidase inhibitor AVE7688 (30 mg/kg/d in chow, n=46), or placebo (n=47) and followed up until they died. After six months, both ramipril and AVE7688 had markedly reduced plasma ACE activity, normalised blood pressure (BP), reduced left ventricular mass and improved systolic function to similar extents. Acetylcholine mediated relaxation of aortic rings was improved by both ramipril and AVE7688. There was substantial albuminuria in the placebo group (albumin-to-creatinine ratio 107+/-54 microg/mg), which was significantly reduced by ramipril to 57+/-34 microg/mg, and practically abolished in the AVE7688 group (22+/-12 microg/mg, p<0.05 vs. placebo and ramipril). Tubulo-interstitial damage (semi-quantitative score) was significantly reduced by AVE7688 and ramipril. Overall mortality was markedly reduced in the ramipril and AVE7688 groups (13% and 16% at six months, respectively), both p<0.05 vs. placebo (71%).CONCLUSIONS:
Vasopeptidase inhibition effectively controls BP and reduces myocardial, vascular and renal target organ damage, resulting in a markedly prolonged survival. At similar degrees of plasma ACE inhibition, AVE7688 compared to ramipril offers superior protection against hypertensive kidney damage.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
/
Inibidores de Proteases
/
Pressão Sanguínea
/
Compostos Heterocíclicos com 3 Anéis
/
Hipertensão
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Renin Angiotensin Aldosterone Syst
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Alemanha