Hemodynamic effects of terlipressin and octreotide administration alone or in combination in portal hypertensive rats.
OBJECTIVE
The action sites and kinetic effects of octreotide and terlipressin may be different. Therefore, we studied the hemodynamic effects of acute administration of these drugs alone or in combination in rats with portal hypertension due to portal vein ligation.


METHODS
In a first study performed in anesthetized rats, hemodynamics were measured before and after drug administration (placebo, octreotide: 8 microg x kg(-1) x h(-1) for 30 min, terlipressin: 50 microg/kg bolus, terlipressin + octreotide at the same doses). The second study, performed in conscious rats, included the same groups and drug doses; hemodynamics were measured every 10 min for 1 h. The third study tested the effect of preinfusion of octreotide on responsiveness to terlipressin.


RESULTS
Terlipressin produced more marked systemic effects than octreotide by decreasing heart rate and cardiac output and increasing mean arterial pressure. Terlipressin produced a greater decrease in portal pressure than octreotide: placebo: -3+/-5%, terlipressin: -42+/-8%, octreotide: -16+/-10%, combination: -44+/-8% (conscious rats at 20 min, p<10(-4)). The decrease in portal pressure was immediate and lasted at least 60 min with both drugs. Octreotide significantly decreased spleno-renal shunt blood flow (% variation): placebo: -6+/-8, terlipressin: -15.5+/-20, octreotide: -22.5+/-20, combination: -27+/-10 (p<10(-2)). Octreotide preinfusion significantly increased the responsiveness of arterial pressure and heart rate to terlipressin.


CONCLUSIONS
Terlipressin decreases portal pressure significantly more than octreotide, while only octreotide significantly decreases collateral blood flow. Simultaneous administration of these drugs does not have significant additive effects but has complementary effects. The preadministration of octreotide alters systemic response to terlipressin.
Oberti
F
F
Laboratoire d'Hémodynamique Splanchnique, Université d'Angers, France.
Veal
N
N
Kaassis
M
M
Pilette
C
C
Rifflet
H
H
Trouvé
R
R
Calès
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D008236:Lypressin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D000077585:Terlipressin
D000959:Antihypertensive Agents; D008236:Lypressin; D000077585:Terlipressin; D015282:Octreotide