Effects of prostaglandin E 1, Isoproterenol and forskolin on cyclic AMP levels and tension in rabbit aortic rings

Abstract

The role of cyclic AMP in the control of vascular smooth muscle tone was studied by monitoring the effects of prostaglandin E 1 (PGE 1), isoproterenol and forskolin on cyclic AMP levels and tension in rabbit aortic rings. PGE 1, isoproterenol and forskolin all increased cyclic AMP levels in rabbit aortic rings. Isoproterenol and forskolin relaxed phenylephrine-contracted aortic rings, but PGE 1 contracted the rings in the presence or absence of phenylephrine. Isoproterenol relaxed these PGE 1-contracted aortic rings without further change in total cyclic AMP levels, which were already elevated by the PGE 1 alone. Pretreatment with forskolin potentiated the effects of PGE 1 on cyclic AMP levels. PGE 1 caused contradictions in muscles partially relaxed by forskolin, even though very large increases in cyclic AMP levels (30 fold) were produced by PGE 1 in the presence of forskolin. Isoproterenol was able to relax these forskolin-treated, PGE 1-contracted muscles with no further increase in cyclic AMP levels. Thus, there does not appear to be a good correlation between total tissue levels of cyclic AMP and tension in these experiments. Our results suggest that, if cyclic AMP is responsible for relaxation of smooth muscle, some form of functional compartmentalization of cyclic AMP must exist in this tissue.