Role of β2-adrenoceptors (β-AR), but not β1-, β3-AR and endothelial nitric oxide, in β-AR-mediated relaxation of rat intrapulmonary artery

The aim of this study was to analyze beta-adrenoceptor (beta-AR)- mediated relaxation in rat intralobar pulmonary artery. The relaxant responses of beta-AR agonists were characterized using beta-AR antagonists in prostaglandin F-2 alpha( PGF(2 alpha))- precontracted arteries. The role of nitric oxide ( NO) and endothelium in beta-AR- mediated relaxation was also investigated. Isoprenaline ( a non- selective beta-AR agonist) and salbutamol ( a selective beta(2)-AR agonist) induced vasorelaxation. ICI 118551 ( a selective beta(2)-AR antagonist) antagonized the effect of both isoprenaline and salbutamol ( pA(2) values of 9.57 and 9.51 respectively). In contrast, atenolol ( 1 mu M) and CGP 20712A ( 0.1 mu M), two beta(1)-AR antagonists, did not modify the relaxing effect of isoprenaline. The response to isoprenaline obtained in the presence of nadolol ( 10 mu M, a beta(1)/beta(2)-AR antagonist) was not further inhibited by SR 59230A ( 1 mu M, a selective beta(3)-AR antagonist). The non- beta(1)/beta(2)-AR agonists studied ( BRL 37344, SR 58611A, and CGP 12177A) did not elicit vasorelaxation. Relaxation to isoprenaline and salbutamol was unaffected by L- N-G- nitro- argininemethyl ester ( 100 mu M, an inhibitor of NO synthase) or after endothelium removal. These results demonstrate the role of beta(2)-AR in mediating relaxation in rat intralobar pulmonary artery precontracted with PGF2a. They indicate that beta(2)-AR- mediated relaxation in this artery is NO- and endothelium- independent. Furthermore, they do not provide evidence of a relaxant role of either beta(1)-or beta(3)-AR in PGF(2 alpha)- precontracted rat intrapulmonary artery.