Haemodynamic responses to a combination of terlipressin and octreotide in portal hypertensive rats.
BACKGROUND
An enhancement of the haemodynamic effects of terlipressin by octreotide (and vice versa) may be useful in the treatment of portal hypertension. The aim of this study was to investigate the short-term effects of terlipressin, octreotide or a combination of these substances on splanchnic and systemic haemodynamics in rats with portal vein stenosis.


METHODS
Eight rats received an intravenous (i.v.) infusion of isotonic saline (10 microL/min for 15 min). Eight rats received terlipressin first (0.05 mg/kg) and then an i.v. infusion of octreotide (8 micrograms.h/kg for 15 min) 15 min later. Eight other rats first received an i.v. infusion of octreotide and then terlipressin 15 min later. Splanchnic and systemic haemodynamics (radioactive microsphere method) were measured after saline, after terlipressin or octreotide alone, and after the combined treatments.


RESULTS
Terlipressin and octreotide alone significantly decreased portal pressure, portal tributary blood flow and cardiac index. Terlipressin, but not octreotide, significantly increased heptocollateral vascular resistance and arterial pressure. Octreotide administration in rats pre-treated with terlipressin did not change portal pressure, caused portal tributary blood flow to increase and decreased hepatocollateral vascular resistance; it also decreased arterial pressure but not cardiac index. Terlipressin administration in rats pre-treated with octreotide further decreased portal pressure, portal tributary blood flow and increased hepatocollateral vascular resistance; terlipressin increased arterial pressure and further decreased cardiac index.


CONCLUSIONS
In rats with portal vein stenosis, octreotide decreased short-term splanchnic and systemic vasoconstriction due to terlipressin. In contrast, terlipressin enhanced the splanchnic and systemic vasoconstriction due to octreotide. Thus, the haemodynamic responses to the combination of octreotide and terlipressin depend on the order of administration of these substances.
Moreau
R
R
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-24, Hôpital Beaujon, Clichy, France.
Cailmail
S
S
Valla
D
D
Lebrec
D
D
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000627:therapeutic use*; D006975:Hypertension, Portal / Q000188:drug therapy*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D000077585:Terlipressin
D000959:Antihypertensive Agents; D006728:Hormones; D008236:Lypressin; D000077585:Terlipressin; D015282:Octreotide