ABSTRACT
The bronchopulmonary effects of phenylephrine (Phe) and methoxamine (Met) were investigated in vitro on isolated guinea-pig tracheas and lung strips and in vivo on pulmonary airway resistance (Raw) in conscious guinea-pigs. Phe, but not Met, relaxed the isolated trachea precontracted with acetylcholine (ACh); this effect was inhibited by propranolol and ascribed to beta-adrenergic stimulation. In the presence of propranolol, both Phe and Met contracted the isolated trachea (-log EC50 were 3.80 +/- 0.37 and 3.04 +/- 0.25 respectively (n = 5] and this effect was competitively antagonized by phentolamine. Phe and Met contracted the isolated lung strips more strongly than the trachea (-log EC50 were 5.14 +/- 0.23 and 4.30 +/- 0.14 respectively (n = 5]. In contrast with the latter, the maximum response was equivalent to that induced by ACh; this effect was also antagonized by phentolamine. In the conscious guinea-pig, Phe (100 and 300 micrograms/kg) and Met (1 and 3 mg/kg) had no effect on Raw but significantly reduced the bronchoconstriction induced by ACh (25 micrograms/kg), histamine (20 micrograms/kg) and serotonin (15 micrograms/kg); this protective effect was unmodified by propranolol (2 mg/kg), yohimbine (1 mg/kg) or piperoxan (0.3 mg/kg) but was significantly inhibited by prazosin (30 micrograms/kg) or AR- C239 (50 micrograms/kg). These results suggest that alpha-adrenergic vasoconstriction with subsequent shrinkage of the bronchial mucosa is responsible for the protective effect of Phe and Met against ACh-induced bronchoconstriction. In isolated lung strips, vasoconstriction would increase tension.
Subject(s)
Adrenergic alpha-Agonists/pharmacology , Airway Resistance/drug effects , Methoxamine/pharmacology , Muscle, Smooth/physiology , Phenylephrine/pharmacology , Acetylcholine/pharmacology , Animals , Cardiovascular System/drug effects , Drug Interactions , Guinea Pigs , Histamine/pharmacology , In Vitro Techniques , Lung/physiology , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Serotonin/pharmacology , Trachea/physiologyABSTRACT
1 In in vitro experiments adenosine 5'-triphosphate (ATP) and adenosine were found to exert different effects on the guinea-pig isolated trachea depending on whether the trachea had previously been contracted with acetylcholine (ACh) (6.6 x 10(-6) M) or was at resting tone. 2 ATP and adenosine (10(-5) and 10(-3) M) were equipotent in relaxing the precontracted guinea-pig trachea, since concentrations of 1.09 +/- 0.35 and 0.39 +/- 0.16 mM respectively reduced by 25% the ACh-induced contraction. 3 ATP and adenosine (10(-5) and 10(-4) M) caused a moderate contraction of the guinea-pi trachea under resting tone. This effect was antagonized by inhibitors of cyclo-oxygenase (indomethacin 10(-6) M, aspirin 0.3 x 10(-3) M and 3 x 10(-3) M) and of thromboxane synthetase (nictindole 10(-7) M, imidazole 5 x 10(-5) M), which suggests an indirect mechanism of action with release of arachidonic acid derivatives.
