Abstract | AIM: METHODS: Over a period of 8 weeks, the effect of seven constant doses of an ARB, valsartan (4-160 mg/kg per day), on blood pressure and proteinuria taken as a surrogate marker of nephropathy in a hypertensive, type 2 diabetic rat model, the spontaneously hypertensive/NIH-corpulent rat (SHR/NDmcr-cp), was assessed. In this spontaneously hypertensive rat strain, a genetic mutation in the leptin receptor gene is associated with hyperphagia leading to obesity with metabolic syndrome and eventually to nephropathy. RESULTS: No additional blood pressure lowering was observed above 120 mg/kg per day of valsartan, suggesting that a dose of 80-120 mg/kg per day had a maximal effect. Nevertheless, higher doses of valsartan further reduced proteinuria in a dose-dependent fashion suggesting the absence of a maximal dose. Obesity, hyperglycaemia and hypercholesterolaemia were unaffected but hypertriglyceridaemia was partially corrected at various ARB doses. CONCLUSION: ARB improve renoprotection at doses above those required for a maximal effect on blood pressure. The mechanism of the renoprotection obtained at high doses of ARB is yet to be elucidated.
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Authors | Naoto Tominaga, Annie Robert, Yuko Izuhara, Shuichi Ohtomo, Takashi Dan, Kazuo Chihara, Kiyoshi Kurokawa, Charles Van Ypersele de Strihou, Toshio Miyata |
Journal | Nephrology (Carlton, Vic.)
(Nephrology (Carlton))
Vol. 14
Issue 6
Pg. 581-7
(Sep 2009)
ISSN: 1440-1797 [Electronic] Australia |
PMID | 19712258
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Tetrazoles
- Valsartan
- Valine
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(pharmacology, therapeutic use)
- Animals
- Blood Pressure
- Diabetes Mellitus, Type 2
(complications)
- Diabetic Nephropathies
(drug therapy, physiopathology)
- Disease Models, Animal
- Hypertension
(complications)
- Linear Models
- Male
- Proteinuria
(drug therapy)
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Tetrazoles
(pharmacology, therapeutic use)
- Valine
(analogs & derivatives, pharmacology, therapeutic use)
- Valsartan
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