Effect of long-term octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis.
1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 micrograms/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 eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. 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 treatment 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 improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.
Lin
H C
HC
Department of Medicine, Veterans General Hospital-Taipei, Taiwan.
Huang
Y T
YT
Cheng
Y R
YR
Hou
M C
MC
Lee
F Y
FY
Chang
F Y
FY
Tsai
Y T
YT
Lee
S D
SD
D000818:Animals; D003251:Constriction, Pathologic / Q000503:physiopathology; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000503:physiopathology*; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D017082:Portal Pressure / Q000187:drug effects; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; D015282:Octreotide