Effects of prostaglandin E2 on nitric oxide-mediated nonadrenergic noncholinergic relaxations in the guinea-pig tracheal muscle.

摘要

The effects of histamine, prostaglandin (PG) E2 and substance P (SP) on functions of nonadrenergic noncholinergic inhibitory (iNANC) nerves were examined in the guinea-pig tracheal muscle in vitro. In the presence of indometacin (10 mumol/l), atropine (2 mumol/l) and propranolol (1 mumol/l), field stimulation (FS) (1-80 Hz, 1 ms, 30 V for 45 s) was applied to the muscle strip under a condition where the same degree of contraction was produced by each agonist. Magnitudes of FS-induced relaxations were significantly smaller for the case of PGE2- or SP-produced contraction than those for the case of histamine-produced contraction. The FS-induced relaxations at lower stimulus frequencies (1-5 Hz) were suppressed by N omega-nitro-L-arginine methylester (L-NAME) (100 mumol/l) during histamine, although they were not affected by L-NAME during PGE2 or SP. Susceptibility of tracheal muscle to S-nitroso-N-acetylpenicillamine, a donor of nitric oxide (NO), was not different during PGE2 or histamine; it was significantly less during SP. FS-induced relaxation during histamine was suppressed by concomitant administration of PGE2 (10 nmol/l), however, not by concomitant administration of SP (30-100 nmol/l). These results suggest that PGE2 may inhibit release of NO from iNANC nerves in airways, whereas SP may suppress responsiveness of airway smooth muscle to the released NO. Results also indicate a possible involvement of these inflammatory mediators under conditions where airway iNANC nerves are impaired.