Differing actions of the acute administration of propranolol and isosorbide-5-mononitrate on the portal circulation.
BACKGROUND
The aim of this study was to clarify the actions of propranolol and isosorbide-5-mononitrate upon the portal circulation.


METHODS
Portal haemodynamics were assessed in 16 patients with transjugular intrahepatic portosystemic stent shunts. A reverse thermodilution catheter was positioned in the portal vein, and portal vein pressure and portal vein flow were measured directly. The effects of propranolol 80 mg and isosorbide-5-mononitrate 20 mg over 1 h were determined independently.


RESULTS
This demonstrated that propranolol reduced both portal pressure gradient (7.7 +/- 2.3 to 5.5 +/- 2.1 mmHg, P < 0.01) and portal vein flow (925 +/- 123 to 597 +/- 99 mL/min, P = 0.01) significantly, implying a reduction in splanchnic inflow as its main effect. In contrast, isosorbide-5-mononitrate tended to increase portal vein flow (814 +/- 186 to 911 +/- 211 mL/min; P = 0.06) whilst reducing portal pressure significantly (108 +/- 12 to 92 +/- 10 mmHg P = 0.014). This suggests a fall in intrahepatic resistance and provides no evidence for baroreceptor-mediated reflex splanchnic vasoconstriction.


CONCLUSIONS
These drugs act upon different variables contributing to portal hypertension and so they may have a powerful synergistic effect in combination. Direct measurement of portal vein flow is a valuable method for assessing the pharmacological modulation of portal venous inflow.
Department of Medicine, Royal Infirmary of Edinburgh, UK.
E H
EH
Forrest
R
R
Jalan
D N
DN
Redhead
P C
PC
Hayes
D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D011169:Portal Vein / Q000187:drug effects* / Q000378:metabolism; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013153:Splanchnic Nerves / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D011433:Propranolol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate