Isosorbide 5-mononitrate effects on isolated rabbit aorta and vena cava: Relationship between cyclic GMP and relaxation of vascular smooth muscle

Abstract

The effects of isosorbide 5-mononitrate (5-ISMN) on vascular smooth muscle tone and cyclic GMP levels in isolated rabbit aorta and vena cava were compared. 5-ISMN induced concentration-dependent relaxation of noradrenaline-contracted strips of aorta and vena cava. 5-ISMN was over 100 times more potent in eliciting relaxation in vena cava than in aorta. Unlike 5-ISMN, 8-bromo cyclic GMP produced concentration-dependent relaxation with similar potency in both strips. The relaxation induced in both strips by 5-ISMN but not by 8-bromo cyclic GMP was inhibited by pretreatment with 5 × 10 −5 M methylene blue. The 5-ISMN-induced changes in tone of both strips were closely associated with those in cyclic GMP levels. 5-ISMN increased the cyclic GMP levels of both strips in a concentration-dependent manner. 5-ISMN was also considerably more potent in increasing cyclic GMP levels in vena cava than in aorta. This 5-ISMN-induced increases in cyclic GMP levels of both strips were inhibited by pretreatment with methylene blue. These results suggest that cyclic GMP could be involved in the 5-ISMN-induced relaxation of smooth muscle from both aorta and vena cava. Furthermore, the finding that 5-ISMN was more active on vena cava than on aorta both to cause relaxation and increase cyclic GMP levels indicates that cyclic GMP-mediated vasodilatation may be responsible for the pharmacological action of 5-ISMN in vivo.