Acute haemodynamic responses and inhibition of tumour necrosis factor-alpha by pentoxifylline in rats with cirrhosis.
1. Although pentoxifylline has been shown to reduce portal hypertension, the mechanism for this is unclear. Since pentoxifylline decreases tumour necrosis factor-alpha production and since this cytokine may induce vasodilatation per se, a pentoxifylline-induced decrease in tumour necrosis factor-alpha production may limit arterial vasodilatation and decrease portal pressure. The aim of the present study was to examine the effects of pentoxifylline administration on plasma tumour necrosis factor-alpha concentration and haemodynamics in normal and cirrhotic rats. 2. In both groups, systemic and splanchnic haemodynamics and plasma tumour necrosis factor-alpha concentrations were measured before and 120 min after the administration of saline or pentoxifylline (20 mg/kg intravenous bolus). 3. In cirrhotic rats, pentoxifylline significantly decreased portal pressure (24 +/- 13%) and tributary blood flow (33 +/- 30%). On the other hand, pentoxifylline significantly increased vascular resistance in portal and hepatic arterial territories. Systemic haemodynamics were not altered. In normal rats, pentoxifylline significantly decreased portal pressure but induced no other significant changes in splanchnic or systemic haemodynamics. In cirrhotic rats, plasma tumour necrosis factor-alpha concentrations were significantly reduced after pentoxifylline administration but not after saline administration. No significant correlations were found between pentoxifylline-induced changes in tumour necrosis factor-alpha levels and changes in splanchnic haemodynamics. In normal rats, plasma tumour necrosis factor-alpha concentrations significantly decreased after pentoxifylline or saline administration. 4. This study shows that in rats with cirrhosis, pentoxifylline induces a decrease in both portal pressure and plasma tumour necrosis factor-alpha concentrations. These reductions were not correlated however.
Soupison
T
T
Laboratoire d'Hémodynamique Splanchnique, Unité de Recherches de Physiopathologie Hépatique, INSERM U-24, Hôpital Beaujon, Clichy, France.
Yang
S
S
Bernard
C
C
Moreau
R
R
Kirstetter
P
P
D'Almeida
M
M
Cailmail
S
S
Tedgui
A
A
Lebrec
D
D
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D010431:Pentoxifylline