Subscribe to RSS
DOI: 10.1055/s-0030-1269297
The beta2-adrenoceptor agonist terbutaline specifically decreases pulmonary arterial pressure by alpha-adrenoceptor antagonism
Objectives: Beta2-adrenoceptor agonists are important bronchodilators in the treatment of obstructive lung disease. In the present study we investigated the impact of the beta2-adrenoceptor agonist terbutaline on pulmonary arterial pressure.
Methods: The effect of terbutaline on vascular tone was measured in dose-response curves after precontraction with different vasoconstrictors in a wire-myograph. The results were confirmed in lung slices and in the isolated perfused lung model of mouse.
Results: Terbutaline decreased the arterial tone of pulmonary arteries but not aortas in a dose-dependent manner after precontraction with phenylephrine and serotonin; this effect was neither observed after pre-treatment with endothelin nor the thromboxane agonist U46619. Further experiments proved that vasorelaxation by terbutaline was independent from the endothelium and the eNOS/NO pathway. Interestingly, beta1- and beta2-adrenoceptor inhibitors had no impact on terbutaline-induced vasodilation in pulmonary artery. However, treatment with the alpha1-adrenoceptor inhibitor phentolamin and Schild-plot analyses revealed that terbutaline acts as an antagonist at alpha-adrenoceptors and thereby relaxes pulmonary arteries. Vasorelaxation by terbutaline was found to be physiologically relevant as it occurred in both, main pulmonary artery and small vessels of lung slices as well as in the isolated perfused lung model.
Conclusion: We conclude that besides its bronchodilating effect terbutaline specifically decreases pulmonary arterial vascular tone. This pharmacological action could be an interesting therapeutic option for the treatment of pulmonary arterial hypertension.