title: Prostanoids and phosphodiesterase inhibitors in experimental pulmonary hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis, characterized by intimal lesions, medial hypertrophy, and adventitial thickening of precapillary pulmonary arteries. Several approved therapies are currently available for the treatment of PAH, of which intravenous epoprostenol is the best explored over the past decade. Newly available oral endothelin receptor antagonists, although clinically efficacious, bear the risk of liver toxicity in a significant portion of patients. Substances that stimulate the formation of the second messengers cyclic adenosine monophosphate (cAMP) or guanosine monophosphate (cGMP) have proved useful in the treatment of various forms of pre-capillary pulmonary hypertension. These second messengers of the endogenous vasodilator mediators that include prostacyclin and nitric oxide (NO) are hydrolyzed by cyclic nucleotide phosphodiesterases (PDEs), a class of enzymes from which 11 isoforms have been characterized. This chapter highlights developments in the treatment of experimental pulmonary hypertension with special attention to prostanoids and PDE inhibitors. We summarize findings for the acute vasodilatory as well as chronic effects of prostanoids, PDE inhibitors, or combinations of both, in animal models of pulmonary hypertension.
authors.affiliation: Department of Internal Medicine II, Justus-Liebig University Giessen, 35392 Giessen, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Theo Schermuly
authors.forename: Hossein
authors.initials: H
authors.lastname: Ardeschir Ghofrani
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011453:Prostaglandins / Q000627:therapeutic use*
chemical_list: D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins