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 notably mitigates the rise in Smad2 mRNA expression and reduces collagen volume fraction levels relative to vehicle-treated mice. This treatment, administered over four weeks at 10 mg/kg/day orally, elevates p-eNOS and eNOS protein levels in SHR aortae without affecting those in WKY aortae. Additionally, it effectively hinders increases in left ventricular weight, the left ventricular weight/body weight ratio, mean myocyte diameter, and the expression of hypertrophic markers ANP and β-MHC, compared to vehicle-treated controls. AVE 3085 significantly enhances ACh-induced endothelium-dependent relaxations in SHR aortae and decreases systolic blood pressure in SHRs. Treatment with AVE 3085 also markedly improves cardiac function indicators such as EFs, FSs, mitral E velocity, E/A ratio, and LVDds, alongside significantly upregulating eNOS protein expression, when compared to the AB group treated with a vehicle.