AVE-3085 is a potent enhancer of endothelial nitric oxide synthase, and used for cardiovascular disease treatment.

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 it also increases the eNOS expression in WKY aortae[3]. Pre-incubation with AVE3085 restores the bradykinin-induced relaxation, reverses the decrease of p-eNOSSer1177, and loares the level of p-eNOSThr495 and nitrotyrosine. NO release in response to bradykinin is significantly reduced by ADMA and such reduction is restored by AVE3085.

AVE 3085 treatment attenuates the increase in the expression of Smad2 mRNA and it also attenuates the collagen volume fraction levels compared to the vehicle-treated mice. 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]. AVE 3085 (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. 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. In the AVE 3085-treated mice, the EFs, FSs, mitral E velocity, E/A ratio and LVDds are significantly improved compared to the vehicle-treated mice. Furthermore, the levels of the eNOS protein expression are significantly up-regulated in the AVE 3085 group than in the vehicle-treated AB group[1].