Atriopeptin III induces endothelium-independent relaxation and increases cGMP levels in rabbit aorta

Atriopeptin III (AP III) is a 24 amino acid synthetic peptide and a fragment of the atrial natriuretic factor. Using isolated rabbit aortic segments with intact or functionally destroyed endothelium, the effect of AP III on muscular relaxation was examined. cAMP- and cGMP levels were also determined. Aortic segments were pre-contracted with norepinephrine 10(-8) M, angiotensin II 10(-7) M or potassium chloride 20 mM. Addition of AP III (10(-10)-10(-7) M) to these pre-contracted segments exerted a concentration-dependent relaxation which was independent of intact endothelium, with EC50 values of 2.2 X 10(-9) M, 2.0 X 10(-9) M and 3.1 X 10(-8) M, respectively. In aortic segments with functionally destroyed endothelial surface, basal levels of cGMP were lower compared with intact vascular tissue. The process of relaxation, induced by AP III, was associated with marked increases of cGMP in intact vascular tissue. cAMP levels were unchanged in both preparations. Our results suggest that AP III elicits a direct, endothelium-independent vascular relaxation associated with increased levels of cGMP in tissue with intact endothelium. Extrusion of intracellular Ca++ by activation of cGMP-dependent protein-kinase may be part of the vasorelaxant profile of AP III.