Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.
BACKGROUND
Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP.


RESULTS
Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration.


CONCLUSIONS
In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.
School of Allied Health Sciences, Faculty of Medicine, Osaka University, Japan. ishikura@sahs.med.osaka-u.ac.jp
Fuminobu
F
Ishikura
Shintaro
S
Beppu
Toshihiko
T
Asanuma
James B
JB
Seward
Bijoy K
BK
Khandheria
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D011687:Purines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009320:Atrial Natriuretic Factor; D000068677:Sildenafil Citrate; D006152:Cyclic GMP