JTV-506, a new K(ATP) channel opener, relaxes pulmonary artery isolated from monocrotaline-treated pulmonary hypertensive rats

Purpose: Vasodilators are considered effective in the treatment of pulmonary hypertension if the vascular reactivity remains reversible. This study was designed to investigate the possibility that JTV-506, a new adenosine trisphoshate-sensitive Potassium Channel opener, may serve as a useful vasodilator in the treatment of pulmonary hypertension.

Methods: After approval by the animal care committee, with the use of the isometric-force recording method, the effects of JTV-506 (1 nM-100 micro M) on the contractile response to norepinephrine (0.1 micro M) were examined in pulmonary arteries isolated from monocrotaline (MCT)-treated (i.e., presumed pulmonary hypertensive) and age-matched control rats. The experiments were performed in the presence of endothelium with or without treatment with N(G)-nitro- l-arginine (L-NAME, 100 micro M), and in its absence.

Results: JTV-506 relaxed ( P < 0.05) norepinephrine-preconstricted, endothelium-intact arteries from MCT-treated and control rats. However, the vasorelaxation was greater ( P < 0.05) in the arteries from MCT-treated rats than in controls. L-NAME treatment attenuated ( P < 0.05) vasorelaxation in the arteries from both MCT-treated and control rats. However, endothelial removal attenuated ( P < 0.05) vasorelaxation only in the arteries from MCT-treated rats and not in control arteries.

Conclusion: 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.