Relaxation of bovine mesenteric arteries by glyceryl trinitrate and other nitro-compounds: evidence for partly different mechanisms of action.

The effect of pertussis toxin (PTX) and the cyclic GMP lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and sodium nitroprusside (SNP) in bovine mesenteric artery (BMA) was investigated. Pretreatment with PTX (100 ng/ml; 2 hr induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN, IS-5-MN or SNP was seen. The relaxatory effect of all the substances tested was markedly reduced by LY83583 (10 microM). The basal cGMP level as well as the GTN induced increase in cGMP were markedly reduced when BMA was exposed to LY83583. The substance also reduced the activation of soluble guanylate cyclase by SNP. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN, IS-5-MN and SNP. As far as the GTN induced relaxation is concerned the sensitivity towards PTX indicates the involvement of regulatory component, possibly a G-protein. However, cyclic GMP seems to play a crucial role in mediating the relaxatory response of all the substances tested since the cGMP-lowering agent LY83583 markedly inhibited the relaxant response induced by all the vascular relaxant agents investigated.