Inhibition of ectonucleotidase with ARL67156 prevents the development of calcific aortic valve disease in warfarin-treated rats.

Calcific aortic valve disease is the most common heart valve disorder. So far, there is no medical treatment for calcific aortic valve disease. The expression of ectonucleotidases, which metabolize nucleotides into phosphate products, may influence the calcification of the aortic valve.

Distinct effects of amlodipine treatment on vascular elastocalcinosis and stiffness in a rat model of isolated systolic hypertension.

Objective: Medial elastocalcinosis (MEC) contributes to the development of large artery stiffness and isolated systolic hypertension. Since endothelin receptor antagonists can prevent and regress elastocalcinosis, our aim was to determine whether amlodipine, a calcium channel blocker that inhibits endothelin signaling, could likewise influence MEC, or reduce pressure mainly through its vasorelaxing properties.

Methods: Control male Wistar rats were compared with rats receiving warfarin (20 mg/kg per day) with vitamin K1 (15 mg/kg per day) alone (WVK) or in association with amlodipine (15 mg/kg per day) for 4 weeks or during the last week or last 4 weeks of an 8-week WVK treatment (two regression groups).

Regression of medial elastocalcinosis in rat aorta: a new vascular function for carbonic anhydrase.

Background: We sought to determine whether carbonic anhydrase (CA), which plays an important role in bone resorption, contributes to vascular mineral loss induced by an endothelin receptor antagonist.

Methods And Results: Wistar rats were compared with rats receiving warfarin and vitamin K1 (WVK) for 8 weeks alone or in association with the endothelin receptor antagonist darusentan (30 mg/kg per day), the CA inhibitor acetazolamide (100 mg/kg per day), or both for the last 4 weeks. Rats were also treated with WVK for 5 or 6 weeks, and darusentan was added for the last week or last 2 weeks of treatment, respectively.

Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition.

In essential hypertension, conduit arteries present hypertrophic remodeling (increased cross-sectional area), whereas small arteries undergo eutrophic remodeling. The involvement of matrix metalloproteinases (MMPs) and de-adhesion proteins, such as tenascin-C and thrombospondin, has been relatively well characterized in large artery remodeling, but their contribution is not known in small artery remodeling. Rats received N(omega)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day) in their drinking water on days 1, 3, 7, 14, and 28.