Dose-dependecy of clonidine's effects in ascitic cirrhotic rats: Comparison with α1-adrenergic agonist midodrine.

Background. Sympathetic nervous system (SNS) activation decreases fluid delivery to the Henle’s loop and response to diuretics; paradoxically, both α1-adrenoceptor agonists and sympatholytic α2-adrenoceptor agonists are recommended in the management of ascitic cirrhosis. Aims & Methods. We assessed the effects of increasing doses of clonidine (α2-agonist) vs. midodrine (α1-agonist) on renal function, mean arterial pressure (MAP), and hormonal status in rats with ascitic cirrhosis due to 13-week CCl4 administration (groups G1-G5), in comparison with control rats (Gc), rats with ascitic cirrhosis untreated (G6) or treated with daily diuretics (0.5 mg/kg furosemide plus 2 mg/kg K+-canrenoate during the 11th-13th weeks of CCl4) (G7). G1-G5 cirrhotic rats received daily, during the 11th-13th CCl4 weeks: clonidine 0.3 mcg only (G1), diuretics + clonidine 0.2 (G2), 0.5 (G3), or 1 mcg (G4), diuretics + midodrine 1 mg/kg b.w. (G5). Results. Cirrhotic rats in G1 or G2 had higher glomerular filtration rate, renal plasma flow, and natriuresis than cirrhotic rats treated with diuretics (G7) (all P<0.05). The addition of clonidine 0.2 mcg to diuretics (G2 vs. G7) reduced serum norepinephrine (169 ± 71 vs. 523 ± 88 ng/L) and plasma renin activity (12 ± 3 vs. 25 ± 5 ng/mL/h) (all P<0.05). Midodrine did not improve the renal performance in ascitic rats treated with diuretics. In comparison to absolute cirrhotic controls (G6), MAP was lower in G4 and higher in G5 (all P<0.05). Conclusions. Low-dose α2-agonists improve natriuresis and reduce SNS function and hyper-aldosteronism without affecting arterial pressure in experimental ascitic cirrhosis treated with diuretics.