Long-Term Angiotensin II Receptor Blockade Limits Hypertension, Aortic Dysfunction, and Structural Remodeling in a Rat Model of Chronic Kidney Disease.
J Vasc Res
; 53(3-4): 216-229, 2016.
Article
em En
| MEDLINE
| ID: mdl-27880955
ABSTRACT
BACKGROUND/AIMS:
Chronic kidney disease (CKD) is associated with large artery remodeling, endothelial dysfunction and calcification, with angiotensin II (Ang II) a known driver of these pathologies. We investigated long-term Ang II type 1 receptor inhibition with valsartan on aortic function and structure in the Lewis polycystic kidney (LPK) rat model of CKD.METHODS:
Mixed sex LPK and Lewis control (total n = 28) treated (valsartan 60 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups were studied. Functional responses to noradrenaline (NA), potassium chloride and endothelium-dependent and independent relaxations were investigated in vitro using acetylcholine hydrochloride (ACh) and sodium nitroprusside (SNP), respectively. Effects of the nitric oxide synthase (NOS) substrate L-arginine, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin on ACh responses were examined.RESULTS:
In the LPK, valsartan reduced systolic blood pressure and urinary protein, ameliorated exaggerated sensitivity to NA, and normalized endothelium-dependent (ACh-Rmax; 91 ± 7 vs. 59 ± 6%, p = 0.0001) and independent dysfunction (SNP-Rmax; 99 ± 1 vs. 82 ± 7%, p = 0.040), as well as improving NO-dependent relaxation (Rmax; -51 ± 6 vs. -26 ± 9%, p = 0.008). Valsartan also reduced aortic wall hypertrophy, elastin disruption/fragmentation, calcification, media cystic degeneration, and levels of matrix metalloproteinase 9.CONCLUSIONS:
This study highlights the role of Ang II in driving vascular manifestations of CKD and indicates that early treatment can significantly limit pathological changes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta
/
Doenças da Aorta
/
Bloqueadores do Receptor Tipo 1 de Angiotensina II
/
Insuficiência Renal Crônica
/
Valsartana
/
Hipertensão
/
Doenças Renais Policísticas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Vasc Res
Ano de publicação:
2016
Tipo de documento:
Article