Atriopeptin II-induced relaxation of rabbit aorta is potentiated by M&B 22,948 but not blocked by haemoglobin.

We examined the effects of haemoglobin (which inhibits the vascular responses to stimulation of soluble guanylate cyclase) and of M&B 22,948 (which selectively inhibits cyclic GMP phosphodiesterase) on the relaxation induced in rabbit aorta by the atrial natriuretic peptide, atriopeptin II (which stimulates particulate guanylate cyclase). Pretreatment with M&B 22,948 (100 microM) produced a 2.3 fold potentiation of atriopeptin II-induced relaxation of endothelium-denuded rings of rabbit aorta. Pretreatment with haemoglobin (10 microM) had no effect on the relaxation or the 10.9 fold increase in cyclic GMP content induced by atriopeptin II in endothelium-denuded rings of rabbit aorta. The potentiation by M&B 22,948 suggests a causal role for cyclic GMP in mediating atriopeptin II-induced vasodilatation of rabbit aorta. The inability of haemoglobin to block the atriopeptin II-induced rise in cyclic GMP suggests that it does not block stimulation of particulate guanylate cyclase. Thus, it is unlikely that a ferrous haem-containing receptor site is involved in the activation of the particulate form of guanylate cyclase as it is with soluble guanylate cyclase.