RENAL VASOACTIVE MEDIATOR GENERATION IN PORTAL HYPERTENSIVE AND BILE-DUCT LIGATED RATS

Background/Methods: Vasoactive substances may have a role in the patho genesis of functional renal abnormalities in patients with cirrhosis. We determined renal vasoactive mediators in rats with portal hypertens ion since the balance in each part of the kidney between the vasodilat or activity of prostaglandin E(2) and the vasospastic activity of thro mboxane A(2), leukotriene B-4, leukotriene C-4, endothelin-1 and plate let activating factor may determine renal function. Rats with partial portal vein ligation (n=7), complete bile duct ligation (n=6) and sham operated (n=10) were studied. Three weeks following surgery renal fun ction tests, including fractional excretion of sodium [Fe(Na)] were me asured. Rats were anesthetized, splenic pulp pressure was measured, ki dneys were removed, and cortex, medulla and papilla were separated and homogenized for determination of prostaglandin E(2), thromboxane B-2, leukotriene B-4, leukotriene C-4 and endothelin-1 by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation. Results: Pulp pressure was >13 mmHg in portal vein ligat ed and bile duct ligated and 6 mmHg in sham operated rats. In bile duc t ligated rats there was a 70% decrease in Fe(Na) and a significant de crease in cortical and papillary prostaglandin E(2), whereas cortical thromboxane B-2 and platelet activating factor activity in the cortex, medulla and papilla were double that of sham operated rats. A similar but insignificant trend of changes was found in portal vein ligated r ats. Medullary leukotriene B-4 was significantly decreased in bile duc t ligated rats. Papillary leukotriene B-4 was not detected in bile duc t ligated and portal vein ligated rats. Renal leukotriene C-4 generati on in the three groups was either unchanged (papilla) or beyond detect ion (cortex and medulla). Medullary and papillary endothelin-1 in port al vein ligated and bile duct ligated rats were 178%-130% higher than in sham operated rats. A significant negative correlation was found be tween Fe(Na) and cortical and medullary thromboxane B-2 generation and medullary platelet activating factor activity. Conclusions: 1) In bil e duct ligated rats enhanced intrarenal generation of thromboxane A(2) and platelet activating factor may contribute to decreased renal sodi um excretion. 2) The role of decreased intrarenal prostaglandin E(2) a nd increased intrarenal endothelin-1 content in bile duct ligated rats is not yet understood. 3) Renal leukotriene generation is either decr eased or undetected in portal vein ligated and bile duct ligated rats.