Incubated or superfused rat lung parenchymal strip: a valid preparation for direct measurement of beta-responses.

Abstract

Responses to the beta-adrenoceptor agonists isoprenaline (Iso) (non selective), salbutamol (Sal) (beta 2-selective) and noradrenaline (NA) (beta 1-selective) were studied on incubated and superfused rat lung strip. In both conditions, Iso and Sal elicited dose-related relaxations of lung strip and these responses were unaffected by the presence of phentolamine (Phen) 10(-5) M. Contractile responses to NA were obtained when it was used alone whereas in the presence of Phen 10(-5) M, NA elicited relaxant responses. The relative potencies of Iso : Sal : NA (plus Phen) were 100 : 20 : 0.69. This demonstrates that beta 2-adrenoceptor is the predominant beta-subtype involved in responses. Propranolol (10(-4) M) completely abolished the relaxant responses to Iso. However, after the addition of Iso tissue responded normally to drugs acting by other mechanisms. Thus, relaxations were obtained with caffeine and contractions with acetylcholine (AcH) or NA. This shows that responses to Iso are mediated only by beta-adrenoceptors. Propranolol and the selective beta-blocking agents butoxamine (beta 2) and atenolol (beta 1) competitively antagonized the effects of Iso. The Schild plots obtained had slopes which did not differ significantly from -1 and mean pA2 values were: 7.82 for propranolol; 6.32 for butoxamine and 5.22 for atenolol. These experiments were carried out in the absence of catecholamine uptake inhibitors, since in a preliminary set of experiments no significant changes of lung strip responses to Iso were observed in the presence of cocaine (10(-5) M) or corticosterone (10(-5) M). In conclusion, it appears that incubated rat lung strip possesses intrinsic tone and, although it cannot be considered a representative preparation of peripheral airways, it provides a valid model for investigating the direct-effects of drugs which act at beta-adrenoceptors.