Aminoguanidine ameliorates splanchnic hyposensitivity to glypressin in a haemorrhage-transfused rat model of portal hypertension.
1. Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors observed in experimental portal hypertension or in rats with haemorrhagic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressin (a long-acting vasopressin analogue) could enhance its portal hypotensive effect in portal-hypertensive rats with bleeding.2. Portal hypertension was induced by partial portal vein ligation. Fourteen days after operation, systemic and portal haemodynamics were measured in stable or bleeding portal vein-ligated rats receiving intravenous glypressin (0.07 mg/kg) or aminoguanidine (70 mg/kg) followed by glypressin infusion. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or aminoguanidine.3. Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligated rats without bleeding than in those with bleeding (P<0.001). In contrast, glypressin induced similar changes in mean arterial pressure between the two groups (P>0.05). The addition of aminoguanidine significantly potentiated the portal-hypotensive effect of glypressin in bleeding portal vein-ligated rats (P<0.005) without an effect on the changes in mean arterial pressure induced by glypressin infusion (P>0.05).4. Splanchnic hyposensitivity to glypressin exists in a haemorrhage-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.
Chu
C J
CJ
Division of Gastroenterology, Department of Medicine, Veterans General Hospital-Taipei, No 201, Sec 2, Shih-Pai Road, Taipei, Taiwan 11217, Republic of China.
Lee
F Y
FY
Wang
S S
SS
Chang
F Y
FY
Lin
H C
HC
Hou
M C
MC
Wu
S L
SL
Tai
C C
CC
Chan
C C
CC
Lee
S D
SD
D000818:Animals; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage; D006975:Hypertension, Portal / Q000188:drug therapy*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D006146:Guanidines; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin; D019001:Nitric Oxide Synthase; C004479:pimagedine