Efeito relaxante do cloridrato de (2,4-diclorofenil)-2-(isopropilamino) etanol, análogo da clorprenalina, em aorta e traqueia isoladas de rato

Abstract

(2,4-dichlorophenyl)-2-(isopropylamino)ethanol hydrochloride (2CFOH) has structural similarity to chlorprenaline, a substance with bronchodilator action. Therefore, the aim of this work was to characterize the pharmacological activity of 2CFOH in the rat aorta and trachea. Segments of these tissues were added to bath system for isolated organs and isometric contractions were obtained and recorded by data acquisition system. In preserved endothelium aorta preparations, 2CFOH (1-1000µM) induced complete relaxation of phenylephrine contraction (1µM), with EC50 of 19.0 [10.1-35.8] µM. Removal of the endothelium decreased the potency of the relaxing effect (p<0.05, Holm-Sidak test). In aorta contracted with potassium (60mM), 2CFOH (0.01-1000µM) induced concentration-dependent relaxation with EC50 of 26.0 [7.6-88.2] µM, the reversal of the contraction being complete. The non-selective β-adrenergic antagonist propranolol (1µM) did not significantly influence the relaxing effect of 2CFOH on the aorta contracted with Potassium (p>0.05, Holm-Sidak test). On the other hand, propranolol (1µM) decreased the potency of 2CFOH (1-1000µM) in aorta contracted with phenylephrine (1µM) (p<0.05, Holm-Sidak test), because EC50 in the presence of propranolol was 32,7 [20.0-53.4] µM, while in the absence it was 19.0 [10.1-35.8] µM. In tracheal rings contracted with carbachol (1µM), 2CFOH (0.01-300µM) induced relaxation, with EC50 of 17.5 [11.9-25.8] µM. Propranolol significantly reduced the relaxing effect of 2CFOH in trachea (p<0.05; Holm-Sidak test), EC50 of 35.6 [11.6-109.0] µM. Therefore, 2CFOH causes relaxation in both the rat aorta contracted with phenylephrine and potassium, and in trachea contracted with carbachol. The endothelium seems to influence this vasorelaxative effect, and a more potent effect is observed in the presence of endothelium. β- adrenergic receptors appear to be involved in the relaxing mechanism when trachea is contracted with carbachol and when aorta is contracted with phenylephrine but not when contraction in the aorta is induced by potassium.