Lanreotide on collateral response to endothelin-1 and vasopressin in cirrhotic rats.
BACKGROUND
Portosystemic collaterals in cirrhosis are often complicated with hemorrhage. Endothelin-1 (ET-1) and arginine vasopressin (AVP) have been shown to directly constrict collaterals of portal hypertensive rats. Furthermore, octreotide, a long-acting somatostatin analog, enhances ET-1-related collateral vasoconstriction if administered in the perfusate before ET-1 incubation. However, long-term effects of somatostatin analogs on collateral response to ET-1 and AVP remain unclarified. This study investigated the effects of lanreotide (a longer-acting somatostatin analog when compared with octreotide) on the portosystemic collateral vascular reactiveness to ET-1 and AVP in cirrhotic rats.


METHODS
Liver cirrhosis was induced in Sprague-Dawley rats by common bile duct ligation (BDL). On the 33rd day after BDL, rats received 1 intramuscular injection with lanreotide (10 mg/kg) or distilled water. On the 43rd day after BDL, systemic, and portal hemodynamics were evaluated. By an in situ perfusion model, ET-1 (10(-10) - 10(-7) mol/L) and AVP (10(-10) - 3 x 10(-7) mol/L) were applied to assess the collateral responses.


RESULTS
Heart rate, mean arterial pressure, and portal pressure were not modified by lanreotide. Lanreotide pretreatment enhanced collateral vascular response to ET-1 and reached statistical significance at 10(-7) mol/L without inducing changes to AVP.


CONCLUSIONS
Lanreotide augmented the collateral vascular responsiveness to ET-1 but not to AVP in cirrhotic rats.
Huang
Hui-Chun
HC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Wang
Sun-Sang
SS
Lee
Fa-Yauh
FY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Hou
Ming-Chieh
MC
Yang
Ying-Ying
YY
Lee
Shou-Dong
SD
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011168:Portal System / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D019332:Endothelin-1; D010456:Peptides, Cyclic; C060347:lanreotide; D001127:Arginine Vasopressin; D013004:Somatostatin