title: Pulmonary hemodynamic responses to inhaled NO in chronic heart failure depend on PDE5 G(-1142)T polymorphism.
abstract: To evaluate the vasoconstrictor component of PH in CHF by investigating the hemodynamic response to inhaled nitric oxide (iNO) and to determine whether this response was influenced by the phosphodiesterase 5 gene (PDE5) G(1142)T polymorphism. CHF patients underwent right heart catheterization at rest and after 20 ppm of iNO and plasma cGMP and PDE5 G(1142)T polymorphism determinations. Of the 72 included CHF patients (mean age, 53±1 years; mean left ventricular ejection fraction, 29±1%; and mean pulmonary artery pressure, 25.5±1.3 mmHg), 54% had ischemic heart disease. Proportions of patients with the TT, GT, and GG genotypes were 39%, 42% and 19% respectively. Baseline hemodynamic characteristics were not significantly different across PDE5 genotype groups, although pulmonary capillary wedge pressure (PCWP) tended to be lower in the TT group (P=0.09). Baseline plasma cGMP levels were significantly lower in the TT than in the GG and GT patients. With iNO, PVR diminished in TT (-33%) but not GG (-1.6%) or GT (0%) patients (P=0.002); and PCWP increased more in TT than in GT (P<0.05) or GG (P<0.003) patients. The PDE5 G(-1142) polymorphism is therefore a major contributor to the iNO-induced PVR decrease in CHF.
authors.affiliation: Department of Cardiology, all at AP-HP, Groupe Hospitalier Albert Chenevier-Henri Mondor, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Lesault
authors.forename: Soulef
authors.initials: S
authors.lastname: Guendouz
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
authors.forename: Ly
authors.initials: L
authors.lastname: Tu
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Marcos
authors.forename: Aziz
authors.initials: A
authors.lastname: Guellich
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Randé
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Teiger
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot