AVE3085

AVE3085 is a potent endothelial nitric oxide synthase enhancer, used for cardiovascular disease treatment. In Vitro: Pre-incubation with AVE3085 restores the bradykinin-induced relaxation, reverses the decrease of p-eNOS^Ser1177, and loares the level of p-eNOS^Thr495 and nitrotyrosine. NO release in response to bradykinin is significantly reduced by ADMA and such reduction is restored by AVE3085. AVE3085 also prevents the elevation of O₂^.? and ONOO^? levels in coronary arteries exposed to ADMA^[2]. AVE3085 (10 μM) markedly increases ACh-induced relaxations in SHR aortae without affecting those in WKY aortae, and also increases the eNOS expression in WKY aortae^[3]. In Vivo: AVE3085 (10 mg/kg/day, p.o.) treatment prevents the increases in the left ventricular weight, left ventricular weight/body weight ratio, mean myocyte diameter, and the expression of the hypertrophic markers ANP and β-MHC compared to the vehicle-treated mice. AVE 3085 treatment also attenuates the collagen volume fraction levels compared to the vehicle-treated mice. In the AVE3085-treated mice, the EFs, FSs, mitral E velocity, E/A ratio and LVDds are significantly improved compared to the vehicle-treated mice. AVE 3085 treatment attenuates the increase in the expression of Smad2 mRNA. Furthermore, the levels of the eNOS protein expression are significantly up-regulated in the AVE3085 group than in the vehicle-treated AB group^[1]. AVE3085 (10 mg/kg, p.o.) significantly improves ACh-induced endothelium-dependent relaxations in the aortae of SHRs, and reduces systolic blood pressure in SHRs. AVE3085 treatment for 4 weeks increases levels of p-eNOS and eNOS in SHR aortae without affecting levels of eNOS and p-eNOS in WKY aortae^[3].