title: Augmentation of the effects of vasoactive intestinal peptide aerosol on pulmonary hypertension via coapplication of a neutral endopeptidase 24.11 inhibitor.
abstract: A deficiency of the pulmonary vasodilative vasoactive intestinal peptide (VIP) has been suggested to be involved in the pathophysiology of pulmonary hypertension (PH). Supplementation of VIP as an aerosol is hampered by the fact that it is rapidly inactivated by neutral endopeptidases (NEP) located on the lung surface. Coapplication of thiorphan, an NEP 24.11 inhibitor, could augment the biological effects of inhaled VIP alone. A stable pulmonary vasoconstriction with a threefold increase of pulmonary artery pressure was established by application the thromboxane mimetic U46619 in the isolated rabbit lung model. VIP and thiorphan were either applied intravascularly or as an aerosol. VIP caused a significant pulmonary vasodilation either during intravascular application or inhalation. These effects were of short duration. Thiorphan application had no effects on pulmonary vasoconstriction per se but significantly augmented the effects of VIP aerosol. Thiorphan, not only augmented the maximum hemodynamic effects of VIP aerosol, but also led to a significant prolongation of these effects. VIP causes pulmonary vasodilation in a model of acute experimental PH. The hemodynamic effects of VIP aerosol can be significantly augmented via coapplication of an NEP inhibitor.
authors.affiliation: Department of Internal Medicine V, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany; Department of Internal Medicine II, Neuwittelsbach Hospital, Munich, Germany; hanno.leuchte@lmu.de.
authors.forename: Hanno H
authors.initials: HH
authors.lastname: Leuchte
authors.affiliation: Department of Internal Medicine V, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Prechtl
authors.affiliation: Department of Internal Medicine V, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany;
authors.forename: Jens
authors.initials: J
authors.lastname: Callegari
authors.affiliation: Department of Internal Medicine V, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Meis
authors.affiliation: Department of Internal Medicine V, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany;
authors.forename: Shani
authors.initials: S
authors.lastname: Haziraj
authors.affiliation: Department of Internal Medicine II, Neuwittelsbach Hospital, Munich, Germany; Therametrics Group, Thalwil, Switzerland.
authors.forename: Dorian
authors.initials: D
authors.lastname: Bevec
authors.affiliation: Department of Internal Medicine V, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Behr
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D015244:Thiorphan / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D011480:Protease Inhibitors; D014660:Vasoactive Intestinal Peptide; D015244:Thiorphan; D015260:Neprilysin
keywords: lung; pulmonary hypertension; vasoactive intestinal peptide; vasoconstriction