Renal vasoactive mediator generation in portal hypertensive and bile duct ligated rats

Background/Methods: Vasoactive substances may have a role in the pathogenesis of functional renal abnormalities in patients with cirrhosis. We determined renal vasoactive mediators in rats with portal hypertension since the balance in each part of the kidney between the vasodilator activity of prostaglandin E(2) and the vasospastic activity of thromboxane A(2), leukotriene B-4, leukotriene C-4, endothelin-1 and platelet 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 function tests, including fractional excretion of sodium [Fe(Na)] were measured. Rats were anesthetized, splenic pulp pressure was measured, kidneys 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 ligated and bile duct ligated and 6 mmHg in sham operated rats. In bile duct ligated rats there was a 70% decrease in Fe(Na) and a significant decrease 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 rats. Medullary leukotriene B-4 was significantly decreased in bile duct ligated rats. Papillary leukotriene B-4 was not detected in bile duct ligated and portal vein ligated rats. Renal leukotriene C-4 generation in the three groups was either unchanged (papilla) or beyond detection (cortex and medulla). Medullary and papillary endothelin-1 in portal vein ligated and bile duct ligated rats were 178%-130% higher than in sham operated rats. A significant negative correlation was found between Fe(Na) and cortical and medullary thromboxane B-2 generation and medullary platelet activating factor activity. Conclusions: 1) In bile duct ligated rats enhanced intrarenal generation of thromboxane A(2) and platelet activating factor may contribute to decreased renal sodium excretion. 2) The role of decreased intrarenal prostaglandin E(2) and increased intrarenal endothelin-1 content in bile duct ligated rats is not yet understood. 3) Renal leukotriene generation is either decreased or undetected in portal vein ligated and bile duct ligated rats.