In vitro and in vivo vasodilating activity of nitroso derivatives gem-substituted with electron-withdrawing groups

A series of nitroso compounds gem-substituted with electron-withdrawing gro ups (R2C(X)NO, R = alkyl, X = NO2, CN, Cl), were studied for their in vitro and in vivo vasodilating properties as well as for their ability to activa te soluble guanylate cyclase (sGC) in RFL-6 cells. All the compounds, with the sole exception of chloro derivative, display good in vitro vasodilating action and are able to increase the basal level of cGMP. Their potencies a s vasodilators decrease in the presence of oxyhaemoglobin, a scavenger of n itric oxide (NO). The haemodynamic profile of the most interesting compound s, assessed in anaesthetized pigs, is also in line with a release of NO fro m these compounds. (C) 2000 Academic Press.