Acute and chronic haemodynamic effects of naftazone in portal hypertensive rats.
It has been demonstrated that hyperproduction of nitric oxide (NO) plays a major role in the vasodilatation of cirrhosis; thus, the vasodilatation might be reversed by an inhibition of NO production. Experimental studies in isolated aortic rings showed that naftazone inhibits the effects of NO production. The aim of this study was to evaluate the haemodynamic effects of acute and chronic administration of naftazone in rats with portal hypertension. Haemodynamic values were measured either before and 10 min after intravenous administration of 432 microg/kg of naftazone or after 4 days of oral administration of 10 mg/kg per day. Acute administration of naftazone significantly reduced portal pressure in portal vein-stenosed and cirrhotic rats. This reduction was related to a decrease in the resistance of the liver and collateral circulation and it was associated with an increased cardiac output. Oral administration of naftazone significantly decreased portal pressure in rats with portal vein stenosis; this decrease depended on a significant reduction of portal blood flow. In both groups, arterial pressure did not change significantly. These haemodynamic effects differed from those observed following prazosin or propranolol administration. However, these effects were similar but less marked than those observed following N-nitro-L-arginine administration in systemic and splanchnic arterial territories. In conclusion, acute and oral administration of naftazone significantly reduces portal pressure by two different mechanisms in portal hypertensive rats. The exact mechanism has, however, to be elucidated.
Sogni
P
P
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-24, Hôpital Beaujon, Clichy, France.
Yang
S
S
Pilette
C
C
Moreau
R
R
Gadano
A
A
Avenard
G
G
Bloy
C
C
Lebrec
D
D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009285:Naphthoquinones / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D004791:Enzyme Inhibitors; D009285:Naphthoquinones; C005272:naftazone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester