Interaction between prostanoids and nitric oxide in the control of tubularfunction in rats with chronic bile duct ligation

Recent work indicates that both nitric oxide and cyclooxygenase products pl ay an important role in the renal alterations of liver cirrhosis, although the interactions between them have not been completely established. The pur pose of this study was to assess the effect of simultaneous blockade of nit ric oxide synthase and cyclooxygenase in rats with chronic bile duct ligati on and in control, sham-operated rats. Compared with control rats, chronic bile duct ligation rats, 23-25 days after surgery, showed a decreased mean arterial pressure, natriuresis, and kaliuresis, without differences in glom erular filtration rate, and an increased urinary nitrite excretion. Nitric oxide synthesis inhibition by administration of N-G-nitro-L-arginine methyl ester induced, in control rats, an increase in mean arterial pressure, wit hout significant changes in natriuresis or glomerular filtration rate. In c hronic bile duct ligation rats, N-G-nitro-L-arginine methyl eater induced a n increase in mean arterial pressure, natriuresis, and kaliuresis, together with a reduction in urinary nitrite excretion and an increase in prostagla ndin E-2 excretion. Cyclooxygenase inhibition with indomethacin induced in both experimental groups a marked inhibition in urinary prostaglandin E-2 e xcretion without significant changes in Na+ or K+ excretion, and a signific ant increase in urinary nitrite excretion in control rats. N-G-Nitro-L-argi nine methyl ester in addition to indomethacin prevented the indomethacin-in duced increase in nitrite excretion and dramatically reduced sodium excreti on in both experimental groups. Thus, the present study suggests that both nitric oxide and cyclooxygenase products interact in the control of urinary sodium excretion and that each system is activated in the absence of the o ther one.