Role of endogenous platelet-activating factor (PAF) in endotoxin-induced portal hypertension in rats.
To determine the role of platelet-activating factor (PAF) in endotoxin-induced portal hypertension, we performed continuous recording of both blood pressure (BP) and portal venous pressure (PVP) in rats following the administration of intravenous PAF (25 ng/kg), intraportal PAF (25 ng/kg), intraportal endotoxin (2 mg/kg), and intraportal endotoxin (2 mg/kg) for 1 min subsequent to pretreatment with a specific PAF-antagonist (CV-6209, 1 mg/kg, i.v.). Basal resting values of both BP (102.3 +/- 9.3 mmHg) and PVP (7.7 +/- 1.2 mmHg) fell rapidly after intravenous infusion of PAF (BP: 36.7 +/- 5.8 mmHg; PVP: 5.7 +/- 0.8 mmHg) and followed by gradual return. Intraportal PAF infusion elicited a rapid but less severe depression of BP (57.2 +/- 9.4 mmHg) as compared with intravenous PAF infusion, whereas PVP was increased transiently around 4 min after treatment (11.0 +/- 5.3 mmHg). A similar degree of PVP elevation (10.7 +/- 2.0 mmHg) was observed between 8 and 20 min after intraportal administration of endotoxin. Depression of BP was initiated 12 min after endotoxin administration but was not severe (76.6 +/- 12.8 mmHg). CV-6209 significantly alleviated the endotoxin-induced elevation of PVP and completely inhibited the hypotension. These observations suggest that: (i) PAF-induced elevation of PVP is a direct response of the liver to PAF; and (ii) endogenous PAF plays an important role in the endotoxin-induced portal hypertension.
Kitagawa
S
S
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Kubota
Y
Y
Yamaguchi
T
T
Fujimura
K
K
Binnaka
T
T
Tani
K
K
Ogura
M
M
Mizuno
T
T
Inoue
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004731:Endotoxins; D006975:Hypertension, Portal / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D017082:Portal Pressure / Q000187:drug effects; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209