title: The renal effects of droxidopa are maintained in propranolol treated cirrhotic rats.
abstract: OBJECTIVE
  Droxidopa improves hemodynamic and renal alterations of cirrhotic rats without changing portal pressure. We aimed to evaluate the effects of a combined treatment with droxidopa and non-selective beta-blockers or statins in order to decrease portal pressure, while maintaining droxidopa beneficial effects.
  
  
  METHODS
  Acute studies combining droxidopa with carvedilol, propranolol or atorvastatin in four-week bile-duct ligated (BDL) rats and a chronic study combining propranolol and droxidopa for 5 days in CCl4 -cirrhotic rats were performed. Hemodynamic values were registered and biochemical parameters from blood and urine samples analyzed.
  
  
  RESULTS
  Bile-duct ligated rats treated with carvedilol + droxidopa showed no changes in mean arterial pressure (MAP) and portal pressure (PP) compared to vehicles. Atorvastatin + droxidopa combination also failed to reduce PP, but maintained the beneficial increase in MAP and superior mesenteric artery resistance (SMAR) and decrease in blood flow (SMABF) caused by droxidopa. In contrast, the acute administration of propranolol + droxidopa significantly reduced PP maintaining a mild increase in MAP and improving, in an additive way, the decrease in SMABF and increase in SMAR caused by droxidopa. This combination also preserved droxidopa diuretic effect. When chronically administered to CCl4 -cirrhotic rats, propranolol + droxidopa caused a decrease in PP, a significant reduction in SMABF and an increase in SMAR. The combination did not alter liver function and droxidopa diuretic and natriuretic effect, and even improved free water clearance.
  
  
  CONCLUSIONS
  Droxidopa could be effective for the renal alterations of cirrhotic patients on propranolol therapy and the combination of both drugs may balance the adverse effects of each treatment.
authors: Liver Diseases Laboratory, Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Sarai
authors: S
authors: Rodríguez
authors: Imma
authors: I
authors: Raurell
authors: Nahia
authors: N
authors: Ezkurdia
authors: Salvador
authors: S
authors: Augustin
authors: Rafael
authors: R
authors: Esteban
authors: Joan
authors: J
authors: Genescà
authors: María
authors: M
authors: Martell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000069059:Atorvastatin; D001663:Bilirubin / Q000097:blood; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D003404:Creatinine / Q000097:blood / Q000652:urine; D015103:Droxidopa / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009994:Osmolar Concentration; D017082:Portal Pressure / Q000187:drug effects; D011188:Potassium / Q000097:blood / Q000652:urine; D011412:Propanolamines / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D051381:Rats; D012709:Serum Albumin; D012964:Sodium / Q000097:blood / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D006538:Heptanoic Acids; D011412:Propanolamines; D011758:Pyrroles; D012709:Serum Albumin; D000077261:Carvedilol; D012964:Sodium; D011433:Propranolol; D000069059:Atorvastatin; D003404:Creatinine; D015103:Droxidopa; D001663:Bilirubin; D011188:Potassium
keywords: cirrhosis; hepatorenal syndrome; hyperdynamic syndrome; non-selective beta-blockers; portal hypertension; pro-adrenergic drug; statins