title: Type V phosphodiesterase inhibition modulates endogenous immunoreactivities of endothelin-1 and endothelial nitric oxide synthase in pulmonary arteries in rats with monocrotaline-induced pulmonary hypertension.
abstract: We evaluated the effects of oral administration of E4021 (100 mg/kg/day), a type V phosphodiesterase inhibitor, on immunoreactivities of endothelin-1, endothelin receptors, and nitric oxide synthases in pulmonary arteries in a rat model of pulmonary hypertension. Immunoreactivities of endothelin-1 and endothelial nitric oxide synthase were observed significantly less frequently, together with significant reduction of right ventricular overload and medial thickening in rats treated with E4021 than in the control with monocrotaline on day 28. The levels of plasma endothelin-1 and serum nitrite and nitrate were significantly lower in rats that received E4021 than in the control with monocrotaline. Oral administration of E4021 modulates endogenous immunoreactivities of endothelin-1 and endothelial nitric oxide synthase with the improvement or right ventricular overload and medial thickening.
authors.affiliation: Department of Infectious Diseases and Applied Immunology, University of Tokyo, Japan. takahata@ims.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: H
authors.initials: H
authors.lastname: Sumino
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Sakamaki
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Iwamoto
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000284:Administration, Oral; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000378:metabolism
chemical_list: C091517:E 4021; D019332:Endothelin-1; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D011799:Quinazolines; D017466:Receptors, Endothelin; D016686:Monocrotaline; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat