Opioid receptor antagonist promotes angiogenesis in bile duct ligated rats.
OBJECTIVE
Angiogenesis, formation of new capillaries from existing vasculature, plays a pivotal role in different pathological states such as many chronic inflammatory diseases including the chronic liver diseases. There is increasing evidence demonstrating accumulation of endogenous opioids and their role in the pathophysiology and manifestations of cholestasis, the main feature of a number of chronic progressive liver diseases. Hence, we investigated the significance of endogenous opioids in angiogenesis in an experimental model of cholestasis.


METHODS
Cholestasis was induced in male Sprague-Dawley rats by bile duct ligation and resection. Naltrexone, an opioid antagonist (20 mg/kg/day) was administered to cholestatic animals for 22 +/- 1 days. The serial sections from liver tissue were stained with von Willebrand Factor antibody and micro-vessel density was assessed by calculating mean micro-vessel number in three hot spots high power microscopic fields.


RESULTS
Naltrexone treatment in bile duct ligated rats led to a marked increase in the micro-vessel number (6.34 +/- 0.21 vs 5.61 +/- 0.22) (P < 0.05), which had already increased during cholestasis.


CONCLUSIONS
In order to clarify the impacts of opioid system blockade in cirrhosis, our findings demonstrate the promoting role of opioid antagonist in angiogenesis in a rat model of cholestasis.
Faramarzi
Negar
N
Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.
Abbasi
Ata
A
Tavangar
Seyed M
SM
Mazouchi
Marjan
M
Dehpour
Ahmad R
AR
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003135:Common Bile Duct / Q000601:surgery; D004195:Disease Models, Animal; D008026:Ligation; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018847:Opioid Peptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D009271:Naltrexone