Effect of chronic administration of sildenafil on sodium retention and on the hemodynamic complications associated with liver cirrhosis in the rat.
Previous studies demonstrated increased phosphodiesterase-5 (PDE5) activity and expression in the kidneys of rats with liver cirrhosis. Acute intravenous administration of PDE5 inhibitors enhanced sodium excretion in these rats. The aim of the present study was to examine the effects of chronic administration of sildenafil on renal sodium handling and hemodynamics in rats with liver cirrhosis. Male Sprague-Dawley rats underwent bile-duct ligation and excision or sham operation and were housed in metabolic cages throughout the study. Body weight, food intake, water intake and urine volume were measured daily, and plasma samples were obtained twice weekly. Fourteen days following surgery sildenafil or its vehicle (dimethylsulfoxide) were administered (20 mg/kg subcutaneously 3 times/day). Two weeks later, systemic hemodynamics were measured under general anesthesia. Sildenafil enhanced the systemic vasodilatation associated with liver cirrhosis and reduced the arterial pressure. There was no reduction in the glomerular filtration rate, however. Despite these hemodynamic changes, sildenafil prevented the decrease in sodium excretion observed in the bile-duct-ligated group receiving vehicle and markedly increased fractional sodium excretion relative to the other groups. These results suggest that chronic sildenafil administration may help prevent or ameliorate sodium retention in cirrhosis, but that hemodynamic adverse effects may ensue.
Ghali-Ghoul
Rana
R
Department of Pharmacology and Therapeutics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Tahseldar-Roumieh
Rima
R
Sabra
Ramzi
R
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D012964:Sodium / Q000652:urine*; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D012964:Sodium; D000068677:Sildenafil Citrate; D006152:Cyclic GMP