title: Alpha-2A Adrenoceptor Agonist Guanfacine Restores Diuretic Efficiency in Experimental Cirrhotic Ascites: Comparison with Clonidine.
abstract: BACKGROUND
  In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites.
  
  
  OBJECTIVE
  To compare clonidine (aspecific α2-adrenoceptor agonist) to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist), both associated with diuretics, in experimental cirrhotic ascites.
  
  
  RESULTS
  Six groups of 12 rats were studied: controls (G1); controls receiving furosemide and potassium canrenoate (G2); rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3); cirrhotic rats treated (over the 11th-14th CCl4 weeks) with furosemide and canrenoate (G4), furosemide, canrenoate and clonidine (G5), or diuretics and SSP002021R (G6). Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance). In comparison with G4, the addition of clonidine (G5) or guanfacine (G6) to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels.
  
  
  CONCLUSIONS
  α2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time.
authors.affiliation: Division of Gastroenterology, Gradenigo Hospital, Torino, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sansoè
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Aragno
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mastrocola
authors.affiliation: Clinical Biochemistry Laboratory, San Giovanni Battista Hospital, Torino, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Mengozzi
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
mesh_terms: D000322:Adrenergic Agonists / Q000627:therapeutic use*; D000818:Animals; D001201:Ascites / Q000188:drug therapy*; D002191:Canrenoic Acid / Q000008:administration & dosage; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use*; D004357:Drug Synergism; D005355:Fibrosis / Q000188:drug therapy*; D005665:Furosemide / Q000008:administration & dosage; D016316:Guanfacine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry
chemical_list: D000322:Adrenergic Agonists; D004232:Diuretics; D018341:Receptors, Adrenergic, alpha-2; D016316:Guanfacine; D005665:Furosemide; D002191:Canrenoic Acid; D003000:Clonidine