EFFECT OF LONG-TERM OCTREOTIDE AND ISOSORBIDE DINITRATE ON HEMODYNAMICS IN RATS WITH PORTAL-VEIN STENOSIS

1. Both octreotide and isosorbide dinitrate have been shown to have po rtal hypotensive effects in animals with portal hypertension. Moreover , in both animals and humans with portal hypertension, the reduction o f portal pressure was enhanced when nitrovasodilators were combined wi th propranolol or vasopressin. The present study was undertaken to eva luate the effect of long-term administration of octreotide and isosorb ide dinitrate on haemodynamics in rats with portal vein stenosis, 2. P ortal hypertension was induced by portal vein stenosis, Portal hyperte nsive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 mu g/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for e ight consecutive days, starting 1 day before surgery. Haemodynamic val ues were measured using a radioactive microsphere technique, 3. Long-t erm octreotide treatment decreased portal pressure and improved the hy perdynamic circulation. In contrast, long-term administration of isoso rbide dinitrate reduced portal pressure but did not ameliorate vasodil atation, A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatmen t was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improv ed the hyperdynamic circulation together with a more profound reductio n of portal pressure than rats receiving octreotide alone.