Marta Martínez-Casales, Raquel Hernanz, Zoe González-Carnicero, Maria T Barrús, Ángela Martin, Ana M Briones, Patrycja Michalska, Rafael León, Estéfano Pinilla, Ulf Simonsen, María J Alonso
Inflammatory mechanisms and oxidative stress seem to contribute to the pathogenesis of hypertension. ITH13001 is a melatonin-phenyl-acrylate hybrid that moderately induces the antioxidant transcription factor Nrf2 and has a potent oxidant scavenging effect compared to other derivatives of its family. Herein, we investigated the effect of ITH13001 on hypertension and the associated cardiovascular alterations. Angiotensin II (AngII)-infused mice were treated with ITH13001 (1 mg/Kg/day, i.p.) for two weeks. The ITH13001 treatment prevented: 1) the development of hypertension, cardiac hypertrophy and increased collagen and Bnp expression in the heart; 2) the reduction of elasticity, incremental distensibility, fenestrae area, intraluminal diameter and endothelial cell number in mesenteric resistance arteries (MRA); 3) the endothelial dysfunction in aorta and MRA; 4) the plasma and cardiovascular oxidative stress and the reduced aortic NO bioavailability; 5) the increased cardiac levels of the cytokines IL-1β , IL-6 and Ccl2 , the T cell marker Cd3 , the inflammasome NLRP3, the proinflammatory enzymes iNOS and COX-2, the TLR4 adapter protein MyD88 and the NFkB subunit p65; 6) the greater aortic expression of the cytokines Tnfα, Ccl2 and IL-6 , Cd3 , iNOS, MyD88 and NLRP3...
December 21, 2023: Journal of Pharmacology and Experimental Therapeutics