Relaxant effect of oxygen free radicals on rabbit tracheal smooth muscle.
We investigated the effect of exogenously generated superoxide anions (O(2)(-)), hydrogen peroxide (H(2)O(2)) and hydroxyl radicals (.OH) on isolated rabbit tracheal smooth muscle suspended in Krebs-Ringer solution. The ability of oxygen free radicals (OFRs) to affect acetyicholine (Ach)-induced contraction in these muscles was also investigated. OFRs, in general, produced a concentration-dependent relaxation of the tracheal smooth muscle in the doses used. However, in large concentrations, O(2)(-) and H(2)O(2) produced effects which were smaller than those obtained with lower concentrations. The relaxant effects of these oxyradicals were progressive and lasted throughout the 20min observation period. At all concentrations used, the OFRs tended to abolish or reduce Ach-induced contraction in a concentration-dependent manner. O(2)(-) was more potent than H(2)O(2) or DHF in relaxing the Ach-precontracted muscle and in inhibiting the response of the muscle to Ach. OFR-induced relaxation of the Ach-contracted muscle was not due to inactivation of the Ach by OFRs. Relaxation produced by OFRs was greater in preparations with intact epithelium than in those denuded of epithelium. The relaxant effects were blocked by indomethacin, a cyclooxygenase inhibitor. OFRs in the presence of indomethacin produced contraction only in the preparations with intact epithelium, suggesting a release of contractile factor(s) from epithelium. These results suggest that OFRs relax rabbit tracheal smooth muscle. The relaxation appears to be mediated through the synthesis and release of prostaglandins from the epithelium and smooth muscles.
Prasad
Kailash
K
Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, USA. prasadk@sask.usask.ca
Gupta
Jang B
JB
D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000601:surgery; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology*; D011817:Rabbits; D013481:Superoxides / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D016877:Oxidants; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007213:Indomethacin