Non-adrenergic, non-cholinergic regulation of guinea-pig airway smooth muscle-indomethacin-induced changes and segmental differences

Abstract

Several lines of evidence suggest a regulatory role for the non-adrenergic, non-cholinergic (NANC) nervous system in the airways of the guinea-pig and man. We examined NANC frequency-response characteristics (0.2–90 Hz) with respect to segmental differences and effects of cyclooxygenase-inhibition (indomethacin 10 μM). Furthermore, the neurogenic contribution to the contractile and the relaxatory NANC response was quantified with tetrodotoxin (1–10 μM). Frontally opened guinea-pig airway rings (n = 3–7) were used. NANC responses were obtained by electrical field stimulation (0.5 ms; 1200 mA; 240 s). A relaxatory NANC response was demonstrated in the proximal and the distal trachea. A contractile NANC response was demonstrated in the distal trachea and the main bronchus. Indomethacin lowered the baseline tension, decreased the relaxatory and increased the contractile NANC response (p < 0.05; at 0.8 Hz; n = 4). A relationship between the baseline tension and the NANC response is suggested. The relaxatory NANC response was tetrodotoxin-sensitive at 3 Hz stimulation frequency (p < 0.05; n = 3). At this frequency, the contractile NANC response was also mainly tetrodotoxin-sensitive (p < 0.05; n = 6) whereas at 60 Hz a dominant, tetrodotoxin-resistant contraction was demonstrated. The pronounced frequency-response relationship as well as the tetrodotoxin sensitivity at very low frequencies (0.2–1.6 Hz) indicates that tetrodotoxin-sensitive NANC nerves are stimulated optimally at low impulse frequencies.