BACKGROUND AND PURPOSE

In patients with pulmonary hypertension (PH) associated with lung disease and/or hypoxia (Group III), decreased pulmonary vascular tone and tissue hypoxia is therapeutically beneficial. PGE and PGI induce potent relaxation of human bronchi from non-PH (control) patients via EP and IP receptors, respectively. However, the effects of PGE /PGI and their mimetics on human bronchi from PH patients are unknown. Here, we have compared relaxant effects of several PGI -mimetics approved for treating PH Group I with several PGE -mimetics, in bronchial preparations derived from PH Group III and control patients.

EXPERIMENTAL APPROACH

Relaxation of bronchial muscle was assessed in samples isolated from control and PH Group III patients. Expression of prostanoid receptors was analysed by western blot and real-time PCR, and endogenous PGE , PGI , and cAMP levels were determined by ELISA.

KEY RESULTS

Maximal relaxations induced by different EP receptor agonists (PGE , L-902688, and ONO-AE1-329) were decreased in human bronchi from PH patients, compared with controls. However, maximal relaxations produced by PGI -mimetics (iloprost, treprostinil, and beraprost) were similar for both groups of patients. Both EP and IP receptor protein and mRNA expressions were significantly lower in human bronchi from PH patients. cAMP levels significantly correlated with PGI but not with PGE levels.

CONCLUSION AND IMPLICATIONS

The PGI -mimetics retained maximal bronchodilation in PH Group III patients, whereas bronchodilation induced by EP receptor agonists was decreased. Restoration of EP receptor expression in airways of PH Group III patients with respiratory diseases could bring additional therapeutic benefit.