PMID- 25178687
OWN - NLM
STAT- MEDLINE
DCOM- 20150917
LR  - 20151119
IS  - 1532-2971 (Electronic)
IS  - 1090-0233 (Linking)
VI  - 202
IP  - 2
DP  - 2014 Nov
TI  - Effect of the phosphodiesterase type 5 inhibitor tadalafil on pulmonary 
      hemodynamics in a canine model of pulmonary hypertension.
PG  - 334-9
LID - S1090-0233(14)00330-X [pii]
LID - 10.1016/j.tvjl.2014.08.009 [doi]
AB  - Phosphodiesterase type 5 (PDE5) inhibitors are used for treating pulmonary 
      arterial hypertension (PAH) in dogs. The long-acting PDE5 inhibitor tadalafil was 
      recently approved for treatment of PAH in humans. Basic information related to 
      the pharmacological and hemodynamic effects of tadalafil in dogs is scarce. In 
      this study, the hemodynamic effects of tadalafil after intravenous (IV) and oral 
      administration were investigated in a healthy vasoconstrictive PAH Beagle dog 
      model induced by U46619, a thromboxane A2 mimetic. Six healthy Beagle dogs were 
      anesthetized with propofol and maintained with isoflurane. Fluid-filled catheters 
      were placed into the descending aorta to measure systemic arterial pressure and 
      in the pulmonary artery to measure pulmonary arterial pressure (PAP). U46619 was 
      infused via the cephalic vein to induce PAH. IV infusion of U46619 significantly 
      elevated PAP from baseline in a dose-dependent manner. U46619-elevated PAP and 
      pulmonary vascular resistance was significantly attenuated by the simultaneous 
      infusion of tadalafil at 100 and 200 microg/kg/h. Likewise, oral administration of 
      tadalafil at 1.0, 2.0, and 4.0 mg/kg significantly attenuated U46619-elevated PAP 
      in a dose-dependent manner. U46619-elevated systolic and mean PAP decreased 
      significantly 1 h after oral tadalafil administration at 4.0 mg/kg, and this 
      effect was maintained for 6 h. In conclusion, tadalafil had a pharmacological 
      effect in dogs and IV infusion of tadalafil induced pulmonary arterial 
      relaxation, while oral administration of tadalafil decreased PAP. These results 
      suggest that tadalafil may offer a new therapeutic option for treating dogs with 
      PAH.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Hori, Yasutomo
AU  - Hori Y
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan. Electronic 
      address: hori@vmas.kitasato-u.ac.jp.
FAU - Kondo, Chigusa
AU  - Kondo C
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Matsui, Maho
AU  - Matsui M
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Yamagishi, Maki
AU  - Yamagishi M
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Okano, Shozo
AU  - Okano S
AD  - Laboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato 
      University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Chikazawa, Seishiro
AU  - Chikazawa S
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Kanai, Kazutaka
AU  - Kanai K
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Hoshi, Fumio
AU  - Hoshi F
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
FAU - Itoh, Naoyuki
AU  - Itoh N
AD  - Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, 
      Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20140815
PL  - England
TA  - Vet J
JT  - Veterinary journal (London, England : 1997)
JID - 9706281
RN  - 0 (Carbolines)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Vasoconstrictor Agents)
RN  - 742SXX0ICT (Tadalafil)
RN  - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid)
SB  - IM
MH  - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology
MH  - Administration, Intravenous/veterinary
MH  - Administration, Oral
MH  - Animals
MH  - Carbolines/*pharmacology/therapeutic use
MH  - Cross-Over Studies
MH  - Disease Models, Animal
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hemodynamics/*drug effects
MH  - Hypertension, Pulmonary/chemically induced/drug therapy/*physiopathology
MH  - Male
MH  - Phosphodiesterase 5 Inhibitors/*pharmacology
MH  - Random Allocation
MH  - Tadalafil
MH  - Time Factors
MH  - Vascular Resistance/drug effects
MH  - Vasoconstrictor Agents/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Dog
OT  - Hemodynamic
OT  - Phosphodiesterase type 5 (PDE5) inhibitor
OT  - Pulmonary arterial hypertension
OT  - Tadalafil
EDAT- 2014/09/03 06:00
MHDA- 2015/09/18 06:00
CRDT- 2014/09/03 06:00
PHST- 2014/04/09 00:00 [received]
PHST- 2014/08/08 00:00 [revised]
PHST- 2014/08/09 00:00 [accepted]
PHST- 2014/09/03 06:00 [entrez]
PHST- 2014/09/03 06:00 [pubmed]
PHST- 2015/09/18 06:00 [medline]
AID - S1090-0233(14)00330-X [pii]
AID - 10.1016/j.tvjl.2014.08.009 [doi]
PST - ppublish
SO  - Vet J. 2014 Nov;202(2):334-9. doi: 10.1016/j.tvjl.2014.08.009. Epub 2014 Aug 15.