Administered orally at 10 mg/kg/day, AVE3085 mitigates the escalation of left ventricular weight, the ratio of left ventricular weight to body weight, the average myocyte diameter, and the expression levels of hypertrophic markers such as atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) in comparison to mice treated with a vehicle. This treatment similarly lessens collagen volume fraction levels and ameliorates various parameters of cardiac function including ejection fraction (EF), fractional shortening (FS), mitral E velocity, E/A ratio, and left ventricular diastolic dimension (LVDd), relative to vehicle-treated mice. Additionally, AVE3085 attenuates the upsurge in Smad2 mRNA expression and notably elevates eNOS protein expression in comparison to the vehicle-treated aortic banding (AB) group^[1].

When administered at a dose of 10 mg/kg orally, AVE3085 significantly enhances ACh-induced endothelium-dependent relaxations in SHRs' aortae and leads to a reduction in systolic blood pressure in SHRs. A four-week treatment with AVE3085 elevates the levels of phosphorylated eNOS and total eNOS in SHR aortae without affecting the levels of eNOS and phosphorylated eNOS in WKY rat aortae^[3].

Pre-treatment with AVE3085 not only reinstates bradykinin-prompted vasorelaxation but also counteracts the reduction of phosphorylated eNOS at Ser1177, diminishes the phosphorylation levels at Thr495, and reduces nitrotyrosine presence. Moreover, AVE3085 counterbalances the decline in nitric oxide (NO) release triggered by ADMA (asymmetric dimethylarginine), a known inhibitor of eNOS, in response to bradykinin. This compound further obstructs the rise in levels of superoxide (O2.−) and peroxynitrite (ONOO−) in coronary arteries subjected to ADMA^[2].

In vascular studies, AVE3085 at a concentration of 10 μM significantly augments acetylcholine (ACh)-induced vasorelaxation in the aortae of spontaneously hypertensive rats (SHRs) without influencing such responses in Wistar-Kyoto (WKY) rat aortae, while also boosting eNOS expression in WKY rat aortae^[3].