Animal groups

Furosemide, canrenoate, clonidine, and SSP-002021R were dissolved in distilled water to obtain different solutions to be administered orally to the rats in 400 μl of fluid. The animals were divided into six groups of twelve rats: controls receiving no intervention (group G1); controls receiving three times a week for 4 weeks oral furosemide (0.5 mg/Kg b.w.) and oral potassium canrenoate (2 mg/Kg b.w.) (G2); rats with ascitic cirrhosis due to 14-week CCl₄ administration and receiving no active drug (G3); cirrhotic rats treated with oral furosemide (0.5 mg/Kg b.w. three times a week) plus oral potassium canrenoate (2 mg/Kg b.w. three times a week) between the beginning of the 11^th and the end of the 14^th week of CCl₄ (G4); cirrhotic rats treated with oral furosemide, oral potassium canrenoate (see above dosage), and oral clonidine (0.3 mcg three times a week) between the beginning of the 11^th and the end of the 14^th week of CCl₄ (G5); cirrhotic rats treated with oral furosemide, oral canrenoate, and the oral prodrug of guanfacine (SSP002021R, selective α_2A-adrenoceptor agonist, 5 mg/kg b.w. three times a week) between the beginning of the 11^th and the end of the 14^th week of CCl₄ (G6). Dosage of furosemide and potassium canrenoate was patterned on respective standard daily human dosage. A dosage of clonidine 0.3 mcg on alternate days was chosen: previous experiments in this laboratory showed clonidine 0.5 mcg caused arterial hypotension in cirrhotic rats and blunted further the effects of diuretics (unpublished data), and published papers showed the effectiveness of low, non-hypotensive doses of clonidine (75 mcg once or twice daily in adult human cirrhotic patients) [10–12]. The dosage of SSP002021R used in this study was established by the provider of the drug (Shire, Basingstoke, U.K.)