EFFECTS OF VANADATE ON RESPONSES OF GUINEA-PIG ISOLATED TRACHEA TO SPASMOGENS

The effects of vanadate on the contractility of the guinea-pig isolated trachea was examined. Vanadate (0.1 mm) produced a sustained contraction that was abolished in Ca2+-free EGTA (0.1 mm)- containing physiological salt solution but was resistant to verapamil (I mum). Vanadate (0.1 mm) depressed tracheal responses to CaCl2 (in Ca2+-free depolarizing solution), KCl, acetylcholine, histamine and 5-hydroxytryptamine. For vanadate (10 mum), the inhibition of spasmogenic responses only reached statistical significance for histamine and 5-hydroxytryptamine. Caffeine (I mm)-induced spasm (trachea at 20-degrees-C in the presence of indomethacin (2.8 muM)) was not affected by vanadate (10 mum-0.1 mm). Vanadate (0.1 mm) slightly depressed the responses to KCl (50 mm), acetylcholine (I mm), histamine (I mm) or 5-hydroxytryptamine (0.1 mm) observed in Ca2+-free EGTA (0.1 mm)-containing physiological salt solution. Vanadate (0.5 mm) depressed Ca2+ (20 muM)-induced contraction of trachea which had been chemically skinned of its plasmalemmal membranes. The mechanism of the inhibitory effect of vanadate on tracheal responses to a variety of spasmogens remains obscure, but, under in-vitro conditions, vanadate clearly does not induce hyper-reactivity of airway smooth muscle to spasmogens.