SYNERGISTIC INHIBITORY EFFECTS OF ATRIOPEPTIN-II AND ISOPROTERENOL ONCONTRACTION OF RAT AORTIC SMOOTH-MUSCLE - ROLES OF CGMP AND CAMP

Atriopeptin II and isoproterenol acted synergistically to inhibit the phenylephrine-induced contraction of aortic smooth muscle from Wistar- Kyoto (WKY) rats. Thus, a weakly inhibitory concentration of atriopept in II (10 nM) caused a 5-fold decrease in the IC50 of isoproterenol fr om 169 nM to 32 nM, whereas a low concentration of isoproterenol (100 nM) increased the maximum inhibition attributable to atriopeptin II fr om 43% to 74%. Atriopeptin TI(10 nM) increased the cGMP found in aorti c smooth muscle and approximately doubled the accumulation of cAMP cau sed by isoproterenol. The results suggest that cGMP, formed by the act ion of atriopeptin II on receptor guanylyl cyclase (GC-A), may inhibit aortic cyclic nucleotide phosphodiesterase type III (PDE III) and tha t an increased accumulation of cAMP then mediates the observed synergi sm.