NO+ but not NO radical relaxes airway smooth muscle via cGMP-independent release of internal Ca2+

We compared the effects of two redox forms of nitric oxide, NO+ [liberated byS-nitroso-N-acetyl-penicillamine (SNAP)] and NO ⋅ [liberated by 3-morpholinosydnonimine (SIN-1) in the presence of superoxide dismutase], on cytosolic concentration of Ca2+ ([Ca2+]i; single cells) and tone (intact strips) obtained from human main stem bronchi and canine trachealis. SNAP evoked a rise in [Ca2+]i that was unaffected by removing external Ca2+ but was markedly reduced by depleting the internal Ca2+ pool using cyclopiazonic acid (10− 5 M). Dithiothreitol (1 mM) also antagonized the Ca2+ transient as well as the accompanying relaxation. SNAP attenuated responses to 15 and 30 mM KCl but not those to 60 mM KCl, suggesting the involvement of an electromechanical coupling mechanism rather than a direct effect on the contractile apparatus or on Ca2+ channels. SNAP relaxations were sensitive to charybdotoxin (10− 7 M) or tetraethylammonium (30 mM) but not to 4-aminopyridine (1 mM). Neither SIN-1 nor 8-bromoguanosine 3′,5′-cy...