Effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats.
BACKGROUND
Chronic portal hypertension is associated with the development of portal-systemic collaterals. Long-term octreotide treatment has been shown to enhance the constrictive response to vasopressin in the mesenteric arteries of portal hypertensive rats. This study investigated the effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats.


METHODS
Partially portal vein-ligated rats were divided into two groups to receive subcutaneous injection of either placebo (5% dextrose in water) or octreotide (30 microg kg(-1)) twice daily for 7 days. Two series of experiments were performed to measure: (a) the systemic and portal hemodynamics and cumulative concentration-response curves of collateral vessels to vasopressin (10(-10) to 10(-7 )M) and (b) the slopes of the flow-pressure curves of collaterals (an index of portal-systemic shunting). The cumulative concentration-response curves and flow pressure curves were determined by the in situ collateral perfusion.


RESULTS
Long-term octreotide treatment significantly lowered the portal pressure without changes in the mean arterial pressure. Vasopressin significantly and similarly increased the perfusion pressure of collateral vessels in both the placebo- and octreotide-treated groups. In addition, long-term octreotide treatment exerted no effect on the EC(50) of vasopressin (-8.25 +/- 0.19 vs. -8.20 +/- 0.10, P > 0.05) and the slopes of flow-pressure curves (0.97 +/- 0.02 vs. 0.94 +/- 0.04, P > 0.05) in the collaterals.


CONCLUSIONS
Despite lowering the portal pressure, long-term octreotide treatment did not enhance the vasoconstrictive effect of vasopressin in the collateral vessels of portal hypertensive rats and ameliorate the degree of portal-systemic shunting.
Wang
S-S
SS
Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China. sswang@vghtpe.gov.tw
Chan
C-C
CC
Lee
F-Y
FY
Chang
F-Y
FY
Lin
H-C
HC
Chen
C-T
CT
Huang
H-C
HC
Tai
C-C
CC
Lai
I-N
IN
Lee
S-D
SD
D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004357:Drug Synergism; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D011168:Portal System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014667:Vasopressins / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014667:Vasopressins; D015282:Octreotide