Modulation of Endothelial Inflammatory Signature by an Im-idazo-Pyrazolyl Urea Derivative in a Dynamic In Vitro Model of Hypertension

Current preclinical models struggle to replicate the complex vascular-inflammatory interplay of hypertension. We developed an advanced hypertension model on bioreactors, to better investigate these dynamics and evaluate new therapies. We tested IPU 3l (a p38MAPK inhibitor) against hypertensive stimuli (AngII and mechanical pressure). In our dynamic model, IPU 3l showed context-dependent effects: it reduced AngII-induced IL-6, IL-8, and ET-1 secretion and inhibited NF-κB activation. When combined with mechanical pressure, it also decreased p38MAPK activation, though it was less effective at preventing pressure-driven ET-1 increases. This advanced hypertension model effectively evaluates anti-hypertensive compounds. Results show IPU 3l offers partial protection against vascular damage, warranting further mechanical and derivative studies.