Smooth muscle relaxation and inhibition of responses to pinacidil and cromakalim induced by phentolamine in guinea-pig isolated trachea

A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its α-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24–100% range. However, phentolamine produced 100% relaxation when the tone was induced by histamine, carbachol, 30 mM K + or 124 mM K +. Relaxant EC 50 values ranged from 8 to 50 μM with the highest potency found against histamine-induced contractions. Phentolamine caused no suppression of contractions elicited by prostaglandin F 2α (PGF 2α) or leukotriene C 4 (LTC 4). At a concentration of 100 μM the α 1-adrenoceptor blocker, yohimbine, produded minor inhibition of spasmoge-induced tone, whereas the α 1-adrenoceptor blocker prazosin (up to 10 μM) had no inhibitory effects in the trachealis. Propranolol (1 μM), prazosin (1 μM), yohimbine (100 μM), tetrodotoxin (3 μM), glibenclamide (10 μM), tetraethylammonium (8 mM), 4-aminopyridine (5 mM), procaine (100 μM), dipyridamole (3 μM) or methylene blue (100 μM) did not influence the relaxant responses to phentolamine. In tracheal preparations contracted by PGF 2α or LTC 4, phentolamine (1, 10 and 100 μM) antagonized the relaxant action of the K + channel openers, pinacidil and cromakalim. The concentration—relaxation curves for pinacidil were shifted 30-fold to the right without change in the maximal effects, whereas the maximal cromakalim-induced relaxant responses were markedly suppressed by phentolamine.