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 alpha-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 EC50 values ranged from 8 to 50-mu-M with the highest potency found against histamine-induced contractions. Phentolamine caused no suppression of contractions elicited by prostaglandin F(2-alpha) (PGF(2-alpha) or leukotriene C4 (LTC4). At a concentration of 100-mu-M the alpha(2)-adrenoceptor blocker, yohimbine, produced minor inhibition of spasmogen-induced tone, whereas the alpha(1)-adrenoceptor blocker prazosin (up to 10-mu-M) had no inhibitory effects in the trachealis. Propranolol (1-mu-M), prazosin (1-mu-M), yohimbine (100-mu-M), tetrodotoxin (3-mu-M), glibenclamide (10-mu-M), tetraethylammonium (8 mM), 4-aminopyridine (5 mM), procaine (100-mu-M), dipyridamole (3-mu-M) or methylene blue (100-mu-M) did not influence the relaxant responses to phentolamine. In tracheal preparations contracted by PGF(2)alpha or LTC4, phentolamine (1, 10 and 100-mu-M) 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.