J. Int. Environmental Application & Science, Vol. 4 (2): 146-151 (2009) 146 Lead Acetate Induces Epithelium-Dependent Contraction of Airway Smooth Muscle Ramadan B. Sopi 1,∗ , Kemajl Bislimi 2 , Fetah Halili 2 , Mentor Sopjani 1 , Burim Neziri 1 , Muharrem Jakupi 1 1 Faculty of Medicine, University of Prishtina, Martyr’s Boulevard, Prishtina, Kosovo, 2 Faculty of Mathematical- Natural Science, University of Prishtina, Prishtina, Kosovo Received December 19, 2008; Accepted April 14, 2009 Abstract: The effect of lead acetate on tracheal smooth muscle (TSM) of dog pups was investigated in this study. In addition we studied the role of epithelium and involvement of nitric oxide (NO) in counteracting the effects of lead acetate on TSM as well as the modifying effects of lead acetate on contractile responses of TSM to acetylcholine (ACh) . Tracheal rings were excised and placed in in vitro organ baths. In vitro administration of lead acetate in increasing concentrations (10 -7 –10 -3 M) induced concentration-dependent contraction of TSM. Prior treatment of tissues with a single dose of lead acetate increased the contractile responses of TSM to acetylcholine (ACh) (10 -10 –10 -6 M). In additional tracheal rings the epithelium was denuded, then preparations were treated with lead acetate. Denudation of the epithelium resulted in an increase in lead acetate-induced contraction of TSM. Another set of tracheal rings were preincubated in bathing medium containing bradykinin (BK, 0.4 mM), to activate NOS. Presence of BK reduced contractile responses of TSM to lead acetate. Our data suggest that subacute exposure to lead, induces epithelium- dependent contraction of airway smooth muscle (ASM) probably via modulation of nitric oxide (NO) release. Keywords: airway smooth muscle, contraction, epithelium, lead acetate, nitric oxide, tracheal smooth muscle. Introduction Lead is a toxic metal known to elicit pathophysiological effects in different organ systems. Earlier studies revealed that lead directly induces contraction of vascular smooth muscle (Watts et al., 1995; Tomera & Harakal, 1986; Valencia-Hernandez et al., 2001) and gastrointestinal system smooth muscle (Janin et al., 1985). Lead potentiates sensitivity of the anococcygeus muscle to contractile stimuli in rats (Shah et al. 1987) as well as aortic smooth muscle (Le-Feng et al., 2005; Heydari et al., 2006) of adult rats in response to different stimuli. Recent studies have shown that lead has inhibitory effects on relaxation of smooth muscle to vaso and bronchodilators (Le-Feng et al., 2007; Gupta & Fahim, 2007). There are some proposed and studied possible mechanisms of the action of lead. Chronic exposure to lead inhibits non-adrenergic non-cholinergic (NANC) relaxation in the rat gastric fundus probably via modulation of NO release from NANC nerves and/or by interacting with intracellular signaling mechanisms (Santos et al., 2006). Another publication speculates that lead- induced cytotoxicity in PC12 cells may be mediated by overproduction of NO (Sharifi et al., 2005). Lead also exhibits direct effects on smooth muscle of blood vessels, mediated by inhibition of the activity of the Na-K-ATPase and increases in intracellular Ca 2+ levels as well as interacting with protein kinase C (Hwang et al., 2001; Kramer et al., 1986; Watts et al., 1995). The airway epithelium has been implicated as a possible modulator of airway smooth muscle tension. It acts as a protective barrier for the underlying ASM to guard against noxious substances and it can release relaxant factors such as NO and prostaglandin E 2 (PGE 2 ), to counteract excessive contractions of ASM (Folkerts, 1995). NO is an important endogenous bronchodilator and is generated from the semi-essential aminoacid L-arginine by the enzyme NO synthase (NOS), of which three different isoforms have been identified in the airways. Constitutive NOS (cNOS) isoforms are mainly ∗ Correspondence: E-mail: rxs274@yahoo.com ; Tel: +381 38 500 600 ext. 20-35;Fax:+381 38 512-223