CHANGES IN CYTOSOLIC CGMP AND CALCIUM IN AIRWAY SMOOTH-MUSCLE RELAXEDBY 3-MORPHOLINOSYDNONIMINE

Nitrovasodilators relax airway smooth muscle by both guanosine 3',5'-c yclic monophosphate (cGMP)-dependent and cGMP-independent mechanisms a nd by mechanisms that reduce cytosolic calcium concentration ([Ca2+](i )). This study was conducted to determine the relative importance of t hese mechanisms in relaxation of canine tracheal smooth muscle (CTSM) induced by 3-morpholinosydnonimine (SIN-1). We measured 1) the effect of SIN-1 on force, [cGMP](i) and [Ca2+](i), and 2) the ability of meth ylene blue (MB) to antagonize SIN-1-induced relaxation and cGMP accumu lation. The ratio of fura 2 emission fluorescence intensities due to e xcitation at 340- and 380-nm wavelengths (F-340/F-380) was used as an index of [Ca2+](i). In strips contracted with 0.3 mu M acetylcholine ( ACh, n = 8) or 24 mM KCl (n = 8), SIN-1 (1-100 mu M) caused a concentr ation-dependent decrease in force which was correlated with a concentr ation-dependent increase in [cGMP](i). MB (10 mu M) proportionally att enuated both relaxation and cGMP accumulation. In fura 2-loaded strips contracted with 0.3 mu M ACh (n = 7) or 30 mM KCl (n = 7), reductions in force induced by SIN-1 (1-100 mu M) were accompanied by decreases in F-340/ F-380. These findings suggest that in CTSM contracted with A Ch or KCl, SIN-1 causes relaxation which appears to be mediated by cGM P-dependent mechanisms that reduce [Ca2+](i).