Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in proximal rat trachea.

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM) and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.

Contractile responses of proximal and distal trachea segments isolated from rats subjected to immunological stimulation: role of connective tissue mast cells.

1. Anaphylaxis-induced contractions of proximal and distal tracheal segments isolated from 14-day ovalbumin (OA)-sensitized rats were studied. 2. OA-induced contractions in distal segments were significantly greater than those observed in proximal segments. 3. Pretreatment of the rats with compound 48/80 or with sodium cromoglycate (SCG) aerosolization significantly reduced OA-induced contractions of trachea distal segments, whereas the contractions of proximal segments were reduced only by compound 48/80. 4. Mepacrine reduced and indomethacin increased the OA-induced contractions in all tracheal segments. Nor-dihydroguaiaretic acid increased the OA-induced contractions in distal tracheal segments, whereas dazoxiben inhibited the contractions in these same segments; neither of these drugs had any effect on the contractions in proximal tracheal segments. 5. The depletion of connective tissue mast cells and subsequent in vitro treatment with indomethacin increased the OA-induced contractions in both segments. 6. We conclude that the contractions of tracheal muscle from OA-sensitized rats depends on the topographic and anatomical origin of the airway tissue. 7. Mediators released by connective tissue mast cells in proximal and distal segments play a pivotal role in this response and may account for variations in the intensity of contraction seen after the addition of OA.