Relationship between nitroglycerin, cyclic GMP and relaxation of vascular smooth muscle

Nitroglycerin (NG) caused a dose dependent-relaxation of the bovine mesenteric artery with an ED 50-value of 2.7 × 10 −8M. The relaxant effect of NG was significantly correlated to an increase in the cGMP content of the artery. There was a significant non-linear component in the data. At moderate cGMP levels relaxation and cGMP changes were correlated. At high levels of cGMP, however, the mechanism responsible for the nitroglycerin-mediated relaxation seemed to be completely activated and a further increase in cGMP did not induce additional relaxation. The cGMP content of the preparation was not significantly changed by nitroglycerin. The cGMP increase induced by nitroglycerin preceded the relaxation. A maximal increase of cGMP was observed after 2 min and the levels subsequently declined. This decline was not accompanied by an increase in the tissue tension. It is suggested from these experiments that cGMP might cause a relaxation of the vascular smooth muscle. Furthermore, if this suggestion is true, there seems to exist a “receptor reserve” for NG with respect to its relaxing action, since an over-capacity for cGMP production is present.