PMID- 15505498
OWN - NLM
STAT- MEDLINE
DCOM- 20050516
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 44
IP  - 5
DP  - 2004 Nov
TI  - Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary 
      hypertension secondary to heart failure through enhancing the natriuretic 
      peptides-cGMP pathway.
PG  - 596-600
AB  - In advanced heart failure (HF), the compensatory pulmonary vasodilation is 
      attenuated due to the relative insufficiency of cGMP despite increased secretion 
      of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent 
      cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We 
      orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 
      7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 
      bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), 
      cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after 
      injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under 
      treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared 
      with the vehicle group despite low plasma ANP levels associated with improvement 
      in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP 
      levels in both groups, whereas it did not change all hemodynamic parameters in 
      the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly 
      increased pulmonary arterial pressure and pulmonary vascular resistance. These 
      results indicated that long-term treatment with a PDE5 inhibitor improved 
      pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to 
      this therapeutic effect.
FAU - Yamamoto, Takashi
AU  - Yamamoto T
AD  - Department of Cardiovascular and Respiratory Medicine, Shiga University of 
      Medical Science, Otsu, Shiga, Japan.
FAU - Wada, Atsuyuki
AU  - Wada A
FAU - Tsutamoto, Takayoshi
AU  - Tsutamoto T
FAU - Ohnishi, Masato
AU  - Ohnishi M
FAU - Horie, Minoru
AU  - Horie M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (HS 142-1)
RN  - 0 (Isoquinolines)
RN  - 0 (Natriuretic Peptides)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Polysaccharides)
RN  - 0 (Pyridines)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterases)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
RN  - EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor)
RN  - H2D2X058MU (Cyclic GMP)
RN  - H68FTS7316 (T 1032)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 3',5'-Cyclic-GMP Phosphodiesterases
MH  - Administration, Oral
MH  - Animals
MH  - Atrial Natriuretic Factor/blood
MH  - Blood Pressure/drug effects
MH  - Cardiac Output/drug effects
MH  - Cardiac Pacing, Artificial/methods
MH  - Cyclic GMP/antagonists & inhibitors/*metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5
MH  - Disease Models, Animal
MH  - Dogs
MH  - Drug Administration Schedule
MH  - Drug Evaluation, Preclinical/methods
MH  - Heart Failure/*complications/drug therapy
MH  - Heart Rate/drug effects
MH  - Heart Ventricles/drug effects/physiopathology
MH  - Hypertension, Pulmonary/*complications/*drug therapy/prevention & control
MH  - Injections, Intravenous
MH  - Isoquinolines/blood/pharmacology
MH  - Japan
MH  - Lung/blood supply/drug effects
MH  - Myocardial Contraction/drug effects
MH  - Natriuretic Peptides/*metabolism/therapeutic use
MH  - Norepinephrine/blood
MH  - Phosphodiesterase Inhibitors/pharmacology/*therapeutic use
MH  - Phosphoric Diester Hydrolases/metabolism
MH  - Polysaccharides/adverse effects/blood/therapeutic use
MH  - Pyridines/blood/pharmacology
MH  - Receptors, Atrial Natriuretic Factor/administration & dosage/antagonists & 
      inhibitors/therapeutic use
MH  - Time Factors
MH  - Vascular Resistance/drug effects
EDAT- 2004/10/27 09:00
MHDA- 2005/05/17 09:00
CRDT- 2004/10/27 09:00
PHST- 2004/10/27 09:00 [pubmed]
PHST- 2005/05/17 09:00 [medline]
PHST- 2004/10/27 09:00 [entrez]
AID - 00005344-200411000-00013 [pii]
AID - 10.1097/00005344-200411000-00013 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2004 Nov;44(5):596-600. doi: 
      10.1097/00005344-200411000-00013.