Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction
| Autor: | Jean-Paul Clozel, Marc de Gasparo, Patrick Hess, Patrick Bruneval, Barbara Nuesslein-Hildesheim |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Medicine (General) Endothelium Tetrazoles Renal function Angiotensin-Converting Enzyme Inhibitors Blood Pressure 030204 cardiovascular system & hematology Pharmacology Nephrotoxicity 03 medical and health sciences R5-920 0302 clinical medicine Endocrinology Enalapril Rats Inbred SHR Internal Medicine medicine Animals Endothelial dysfunction Aldosterone Antihypertensive Agents Dose-Response Relationship Drug biology business.industry Valine Angiotensin-converting enzyme medicine.disease Survival Analysis Angiotensin II Rats Drug Combinations medicine.anatomical_structure Valsartan Creatinine Hypertension biology.protein Endothelium Vascular business medicine.drug |
| Zdroj: | Journal of the Renin-Angiotensin-Aldosterone System, Vol 1 (2000) |
| ISSN: | 1752-8976 1470-3203 |
| Popis: | There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy. SHR were treated with either the angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II) AT1-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the effects on survival rates, cardiac and renal changes were monitored. Rats treated with valsartan, alone or in combination with enalapril, showed markedly higher survival rates (67—85%, respectively) than untreated animals (37%) or those treated with enalapril alone (55%). Valsartan at a dose which attenuated blood pressure increase led to even greater survival rates (95%). Despite these improved survival rates, at non-hypotensive doses the drugs had no effect on histological appearance, nor was kidney function improved. Plasma creatinine levels were reduced by valsartan, alone or in combination with enalapril, but proteinuria persisted with all treatments over the 12 weeks of the study. Aldosterone levels were significantly reduced by all treatments. The results suggest a beneficial role for endothelium in hypertension. Reduced renal perfusion pressure probably underlies the beneficial renal effects of high-dose valsartan. |
| Databáze: | OpenAIRE |
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