Selective Kallikrein Inhibitors Attenuate Hemorrhagic Lesions Caused by Kinin Antagonists in Experimental Acute Pancreatitis
作者单位：Institute of Experimental and Clinical PharmacologyMedical University of GrazAustria Ferring Research Ltd.SouthamptonUK. Institute of Experimental and Clinical PharmacologyMedical University of GrazAustria
会议名称：《第十五届国际药理学大会》
会议日期：2006年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
摘 要：正 Kinin B2 antagonists prevent edema in acute pancreatitis but also cause hemor-rhagic lesions. We investigated whether this is due to reduced influx of endogenous protease inhibitors and increased tissue kallikrein activity. Pancreatitis was induced in anesthetized rats by i. v. infusion of cerulein. Rats were pretreated with the B2 antagonist icatibant and/or selective inhibitors of tissue kallikrein （TKI） and plasma kallikrein （PKI） [Evans et al.. 1996]. The pancreatic tissue was analyzed for hemoglobin. Icatibant inhibited edema formation but caused apronounced increase in tissue hemoglobin. Although TKI also in- hibited edema, vascular damage was *** caused by icatibant was largely attenuated by combined TKI and PKI. Influx of endogenous protease inhibitors was significantly reduced by icatibant and TKI. Tissue kalli krein activity was increased 10-100 fold by icatibant. but was inhibited by TKI. We conclude that increased levels of active kallikrein in the pancreas cause hemorrhagic lesions when edema is absent. Inhibition of kallikreins thus could be a promising strategy for the prevention of hemorrhagic lesions in acute pancreatitis.