ENDOTHELIUM-DEPENDENT RELAXATION OF RAT THORACIC AORTA BY AMRINONE-INDUCED NITRIC-OXIDE RELEASE

To determine whether amrinone and its induced increase of cyclic AMP r eleases nitric oxide and enhances endothelium-dependent vascular relax ation, we studied nitric oxide production and vascular relaxation of r at thoracic aorta on treatment with amrinone and forskolin, an activat or of adenylate cyclase. When 20 mu M amrinone was applied to ring seg ments of aorta previously contracted with phenylephrine, relaxation wa s greater in segments with endothelium than in those without (% relaxa tion 94 +/- 4 vs 37 +/- 7%, P<0.01). However, a higher concentration o f amrinone (>50 mu M) induced the same degree of relaxation in ring se gments with or without endothelium, probably due to its direct effect on vascular smooth muscle. The maximal relaxant concentration (100 mu M) of amrinone induced an increase (2.5 fold) in cyclic GMP in ring se gments. Forskolin also induced concentration-dependent relaxation, but removal of the endothelium attenuated the relaxation induced by forsk olin about seven-fold. N-G-nitro L-arginine reversed the relaxation in duced by amrinone or forskolin in ring segments with, but not without, endothelium. Nitric oxide production in ring segments of aorta, follo wing application of amrinone or forskolin, was detected by nitric oxid e-selective electrode and electron paramagnetic resonance spin trappin g methods. Pre-treatment with N-G-nitro L-arginine or removal of the e ndothelium suppressed nitric oxide production by amrinone or forskolin .These data showed that amrinone enhances the release of nitric oxide from rat aortic endothelial cells, and induces endothelium-derived rel axing factor/nitric oxide-mediated vasodilation.