2 -Adrenoceptor agonists are widely used in the treatment of pulmonary diseases. We have investigated the relaxant and antiinflammatory activities of Ϫ5 M) elicited a relaxation of human isolated bronchi moderately higher than salbutamol, which was reduced by a -adrenergic blocking drug, propranolol, but not by an inhibitor of guanylate cyclase, ODQ (1H-[1,2,4]oxadiazolo [4,3-] quinolaxin-1-one). The treatment of mice with NCX-950 (1, 10, and 100 M aerosol) markedly inhibited the neutrophil influx induced by LPS aerosol in bronchoalveolar lavage (BAL) fluid, whereas salbutamol at equimolar doses elicited a moderate inhibition. Pretreatment of mice with NCX-950 (100 M) also significantly reduced tumor necrosis factor-␣, interleukin-6 (IL-6), transforming growth factor-, and matrix metalloproteinase-9 release in BAL fluid, whereas salbutamol was ineffective. Propranolol, but not ODQ, suppressed the inhibitory activity of NCX-950 on neutrophil influx and IL-6 release in BAL fluids. A nitric oxide-releasing sildenafil NCX-911 [(5-[2-ethoxy-5-(4-methylpiperidinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3-d]pyrimidin-7-one nitrate)], but not sildenafil (100 M) also reduced the neutrophil influx following LPS exposure in mice. This study reported that NCX-950 elicits potent relaxant and anti-inflammatory activities compared with salbutamol, and these effects may be mainly due to the activation of the  2 -adrenoceptor rather than the cGMP pathway.