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 groups (R(2)C(X)NO, R=alkyl, X=NO(2), CN, Cl), were studied for their in vitro and in vivo vasodilating properties as well as for their ability to activate 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 as vasodilators decrease in the presence of oxyhaemoglobin, a scavenger of nitric oxide (NO). The haemodynamic profile of the most interesting compounds, assessed in anaesthetized pigs, is also in line with a release of NO from these compounds.
Di Stilo
A
A
Dipartimento di Scienza e Tecnologia del Farmaco, Universita di Torino, via P. Giuria 9, Torino, 10125, Italy.
Medana
C
C
Ferrarotti
B
B
Gasco
A L
AL
Ghigo
D
D
Bosia
A
A
Martorana
P A
PA
Gasco
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D004583:Electrons; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D014665:Vasodilator Agents; D006162:Guanylate Cyclase; D006152:Cyclic GMP