Key result
Simvastatin plus losartan blunts salt-induced hypertension but impairs losartan's benefit on vascular reactivity.
Why the study?
The renin-angiotensin-aldosterone system and oxidative stress play a major role in the pathogenesis of hypertension, but the effects of simvastatin and losartan on these pathways in salt-induced hypertension were not fully characterized.
Does simvastatin, losartan, or their combination reduce blood pressure and oxidative stress in a rat model of salt-induced hypertension?
Does simvastatin, losartan, or their combination reduce blood pressure and oxidative stress in a rat model of salt-induced hypertension?
In a rat model of salt-induced hypertension, both simvastatin and losartan reduced oxidative stress and blood pressure, but their combination impaired losartan's beneficial effects on vascular reactivity.
Animal data link both agents to lower oxidative stress and BP; leaves open whether combination is additive or contraindicated in salt-sensitive hypertension.
BACKGROUND: The renin-angiotensin-aldosterone system and oxidative stress play a major role in the pathogenesis of hypertension. METHODS: We examined the effects of simvastatin, an HMG-CoA inhibitor, and losartan, an angiotensin type 1 receptor antagonist, in Dahl rats fed a high salt diet (8% NaCl), and treated with either simvastatin (3 mg/kg/d), losartan (10 mg/kg/d), or their combination using the drinking water as vehicle, for 3 weeks. Mean blood pressure (MAP) was measured by tail-cuff plethysmography. Plasma levels of nitric oxide (NO) and prostanoids, as well as plasma and tissue angiotensin II (Ang II) and aldosterone (ALDO) were analyzed by enzyme immunoassay. Renal and aortic superoxide production was determined by fluorescence spectrometry. Vascular reactivity of second-order mesenteric arteries was assessed in vitro. RESULTS: Simvastatin, losartan, and the drug combination attenuated the salt-induced increase in MAP. Plasma NO was elevated by simvastatin, losartan, and the combination, whereas plasma thromboxane was reduced by losartan. Simvastatin, losartan, and the combination reduced renal Ang II, but only the combination reduced cardiac Ang II. Heart and renal ALDO were reduced by simvastatin, losartan, and the combination. Aortic and renal NADPH-dependent superoxide production was reduced by simvastatin, losartan, and the combination. The response to acetylcholine, in mesenteric arteries preconstricted with norepinephrine, was greater in the losartan group. CONCLUSIONS: Thus, treatment with simvastatin and losartan lowered oxidative stress and improved endothelial function. Simvastatin significantly reduced the effect of losartan on vascular reactivity in mesenteric arteries, suggesting that their combination may be contraindicated.
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Bayorh et al. (2005) studied Salt-induced hypertension. Simvastatin, losartan, or their combination vs. Vehicle (drinking water) was evaluated on Mean blood pressure (MAP), oxidative stress, and endothelial function. Simvastatin and losartan attenuated salt-induced increases in mean blood pressure and lowered oxidative stress, but their combination reduced losartan's effect on vascular reactivity.
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