Calcium-channel blocker attenuates kupffer cell production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion in rat liver

We investigated the effects of the calcium-channel blocker verapamil hydroc hloride on the production of cytokine-induced neutrophil chemoattractant (C INC) following reperfusion injury in rat liver. Ischemia was induced for 30 min by portal vein occlusion. Animals were pretreated with intravenous inj ection of verapamil hydrochloride (2.5 mg/kg) 5 min before vascular clamp. Verapamil hydrochloride limited increases in the chemoattractant compared w ith nonpretreated rats. Most cells immunostained for chemoattractant were E D2-positive macrophages in sinusoids. In vitro, chemoattractant production by Kupffer cells isolated from animals pretreated with verapamil hydrochlor ide was significantly lower than by Kupffer cells from nonpretreated animal s. Expression of transcripts in liver for chemoattractant peaked 3 hr after reperfusion in nonpretreated animals, while pretreatment with verapamil hy drochloride significantly decreased chemoattractant mRNA levels. In vitro, chemoattractant production could be induced in naive Kupffer cells after st imulation with oxygen radicals generated by hypoxanthine and xanthine oxida se, but verapamil hydrochloride prevented these increases. We concluded tha t the calcium-channel blocker verapamil hydrochloride significantly attenua tes chemoattractant release by Kupffer cells after ischemia-reperfusion in the rat liver.