Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver.
BACKGROUND
The NO--cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats.


METHODS
Hemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 microg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats.


RESULTS
Cardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 microg/kg was the most effective dose for both PDE-5 inhibitors.


CONCLUSIONS
Low doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated.
Halverscheid
Leonie
L
1Department of Anesthesiology, University Hospital Duesseldorf, Germany. halverscheidl@anesthesia.ucsf.edu
Deibert
Peter
P
Schmidt
René
R
Blum
Hubert E
HE
Dunkern
Torsten
T
Pannen
Benedikt H J
BH
Kreisel
Wolfgang
W
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D023421:Models, Animal; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068677:Sildenafil Citrate