Mechanisms responsible for the resistance of tracheal smooth muscle to histamine in rats

Abstract

A mechanographic study of contractile responses by tracheal smooth muscle segments of rats to a histaminergic agent showed that intact segments did not respond to histamine in the concentrations used (0.01-10 rtM), whereas depolarized segments responded to histamine by dose-dependent contractions which were considerably enhanced following mechanical removal of the tracheal epithelium. Key Words: trachea; smooth muscle; histamineHeightened reactivity of the bronchi is an important pathogenic mechanism of obstructive lung disease [9][10][11]. Among the mediators of bronchospasm, a leading role is played by histamine. Activation of histamine receptors results in the exit of calcium to the cytosol and in muscular contraction. This is a characteristic feature of bronchial smooth muscle cells (SMC) in rabbits and guinea pigs [5,9], in which bronchospastic responses of allergic or inflammatory origin are readily inducible [6].In rats, however, it is virtually impossible to produce bronchospasm by any means. This phenomenon has attracted the attention of many investigators, but has not received a uniquely interpretable explanation [6,9,11].We focused on the observation that tracheal SMC do not respond by contraction to histamine in either physiological or supraphysiological concentrations [5], even though histamine receptors are abundant on the membranes of these ceils.The purpose of the present study was to examine the mechanisms responsible for the resistance of rat tracheal SMC to histaminergic agents. Department of Biophysics, Siberian Medical University, Tomsk MATERIALS AND METHODSCircular segments 3-4 mm wide prepared from the lower parts of tracheas of random-bred male rats were placed in a thermostatically controlled chamber containing a continuously aerated Krebs solution of the following composition (mM): 120.4 NaC1, 5.0 KC1, 1.2 MgCI=, 2.5 CaCI~, 1.2 NaH=PO 4, 15.5 HEPES, and 11.5 glucose (pH 7.35, 37~ This solution was changed every 10 min. In some rats, the tracheal epithelium was removed mechanically [12]. Contractile activity was recorded with a mechanotron under near-isometric conditions. Mechanical tension was estimated in percent of the contractile response to a hyperpotassic (40 mM KC1) Krebs solution. RESULTSThe first series of tests was designed to assess the effect of histamine on the tracheal segments. As shown in Fig. 1, these segments failed to respond to histamine in concentrations of 0.01 to 10 ~tM, but did respond in a dose-dependent manner when 40 mM KC1 were present in the solution. The

Specific features of epithelium-dependent contractile reactions of smooth muscles in various subdivisions of the respiratory tract

“…The state and functional activity of the epithelium strongly influences the contractile responses of SM-segments to catecholamines, cholinomimetic agents, histamine, and other physiologically active substances [5,8,11]. Interaction of these agents with the receptors in the epithelial cell membrane stimulates the synthesis of epithelium-derived relaxing factor which suppresses the contractile activity of SM cells due to activation of guanylate cyclase [3,12].…”