The present study investigates the effects of chronic administration of ACEIs (angiotensin-converting-enzyme inhibitors; either zofenopril or enalapril) in combination with a diruetic (hydrochlorothiazide) on BP (blood pressure) increase and renal injury induced by L-NAME (NG-nitro-L-arginine methyl ester), an inhibitor of NO (nitric oxide) synthesis. Rats were untreated or received L-NAME alone, L-NAME+zofenopril+hydrochlorothiazide or L-NAME+enalapril+hydrochlorothiazide for 8 weeks. L-NAME treatment resulted in marked elevation in BP and mortality. Treatment with either ACEI and diuretic prevented the increase in BP induced by L-NAME, reduced the death rate and improved excretory parameters. Renal injury in the L-NAME group was severe, but, in the groups treated with either ACEI and diuretic, glomerular and tubulointerstitial lesions were not observed and the intensity, number and size of vessels affected was reduced. However, the efficacy of zofenopril+diuretic was superior to that of enalapril+diuretic in reducing vascular alterations. Oxidative stress indices and the expression of NO synthase and nitrotyrosine were normalized by the treatments. In conclusion, the combined treatment of zofenopril or enalapril with hydrochlorothiazide completely prevented the development of arterial hypertension induced by L-NAME. Renal morphological and functional alterations in the hypertensive animals were also almost completely normalized, but the treatment with zofenopril+diuretic produced a more complete organ protection. The protective effect is related to an activation of endothelial NO synthase expression and to a normalization of the oxidative stress parameters due to the inhibition of angiotensin II.
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Research Article|
January 17 2006
Effects of angiotensin-converting-enzyme inhibitors in combination with diuretics on blood pressure and renal injury in nitricoxide-deficiency-induced hypertension in rats
Joaquín García-Estañ;
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
Correspondence: Dr Joaquín García-Estañ (email [email protected]).
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M. Clara Ortiz;
M. Clara Ortiz
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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Francisco O'Valle;
Francisco O'Valle
†Department of Physiology, Faculty of Medicine, University of Granada, 18012 Granada, Spain
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Antonia Alcaraz;
Antonia Alcaraz
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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Esther G. Navarro;
Esther G. Navarro
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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Félix Vargas;
Félix Vargas
†Department of Physiology, Faculty of Medicine, University of Granada, 18012 Granada, Spain
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Stefano Evangelista;
Stefano Evangelista
‡Department of Preclinical Development, Menarini Ricerche spa, Firenze, Italy
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Noemí M. Atucha
Noemí M. Atucha
*Department of Physiology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
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Publisher: Portland Press Ltd
Received:
May 24 2005
Revision Received:
September 15 2005
Accepted:
October 03 2005
Accepted Manuscript online:
October 03 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2006
Clin Sci (Lond) (2006) 110 (2): 227–233.
Article history
Received:
May 24 2005
Revision Received:
September 15 2005
Accepted:
October 03 2005
Accepted Manuscript online:
October 03 2005
Citation
Joaquín García-Estañ, M. Clara Ortiz, Francisco O'Valle, Antonia Alcaraz, Esther G. Navarro, Félix Vargas, Stefano Evangelista, Noemí M. Atucha; Effects of angiotensin-converting-enzyme inhibitors in combination with diuretics on blood pressure and renal injury in nitricoxide-deficiency-induced hypertension in rats. Clin Sci (Lond) 1 February 2006; 110 (2): 227–233. doi: https://doi.org/10.1042/CS20050165
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