JTV-506, a new KATP channel opener, relaxes pulmonary artery isolated from monocrotaline-treated pulmonary hypertensive rats

Abstract

JTV-506 may possibly attenuate pulmonary vascular tone through its direct action on vascular smooth muscle cells. In the presence of MCT-induced pulmonary hypertension, JTV-506 may further attenuate pulmonary vascular tone through its direct action on endothelial cells, possibly by stimulating the endothelial release of NO.

p38 Mitogen-Activated Protein Kinase Mediates the Sustained Phase of Hypoxic Pulmonary Vasoconstriction and Plays a Role in Phase I Vasodilation

“…In cardiac myocytes, p38 MAP kinase inhibition with SB-203580 significantly decreases endotoxin-induced cardiac tumor necrosis factor (TNF)-␣, interleukin (IL)-1␣, IL-1␤, and IL-6 cytokine expression [29]. There is accumulating evidence that p38 MAPK controls inflammatory mediators in renal failure after burn injury [41], TNF expression in the heart (reviewed in [28], lung tissue iNOS expression in endotoxic shock [42], and plasma levels of tumor necrosis factor-related apoptosis-inducing ligand in response to endotoxemia [43]. Although p38 MAPK's effect on cytokine expression in PA rings has not been studied, it is known that TNF-alpha, IL-1, and IL-6 all contribute to pulmonary vasoconstriction, pulmonary hypertension, and HPV [44 -48].…”