In vitro activity: NS-1619 induced concentration-dependent activation of BKCa channels with a calculated EC50 of 32 microM. The NS 1619-induced activity was dependent on the presence of free Ca2+ at the intracellular surface, but was not associated with a change in channel voltage sensitivity. NS 1619 (50 microM) inhibited the noradrenaline-induced contraction. NS 1619 (10-100 microM) reduced the high K+-induced contractions in a noncompetitive manner. Inhalation of a 12 μM and 100 μM NS1619 solution significantly reduced RV pressure without affecting systemic arterial pressure. Blood gas analyses demonstrated significantly reduced carbon dioxide and improved oxygenation in NS1619-treated animals pointing towards a considerable pulmonary shunt-reducing effect. In PASMC's, NS1619 (100 μM) significantly attenuated PASMC proliferation by a pathway independent of AKT and ERK1/2 activation.

Kinase Assay:

Cell Assay: