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Dose-dependent reduction by indomethacin of urinary volume and sodium excretion during furosemide diuresis in consciuos saline-loaded rats
PROSTAGLANDINS
DOSE-DEPENDENT REDUCTION BY INDOCETHACIN OF URINARY VOLUME AND SODIUM EXCRETION DURING FUROSEMTDE DIURESIS IN CONSCIOUS SALINE-LOADEP RATS. BARRETT,
C. and RYAN,
M.P.
Department of Pharmacology University College Dublin BELFIELD, DUBLIN 4. Ireland
Prostaglandins may play an important role in the regulation of renal function. There are indications that the action of diuretics, especially loop-blocking diuretics, can be, at least partly, mediated by renal prostaglandins. Administration of some nonsteroidal anti-inflammatory drugs have been reported to reduce the diuretic efficacy and also the antihypertensive action of diuretic drugs. We have investigated the effects of indomethacin, a non-steroidal anti-inflammatory drug, on urinary volume and sodium excretion during furosemide diuresis in conscious saline-loaded rats. Male Wistar rats, matched by weight, were fasted overnight but allowed free access to water. All experiments were carried out at the same time of the day. Indomethacin (0, 1,3, 10 mg/kg) was administered intraperitoneally in Na CO solution (2 mls/kg). 1 hour later furosemide (40 mg/kg) was giv& arally in 0.9 % NaCl (25 mls/ko). Rats were placed in individual metabolism cages and urine was collected for 5 hours. Food and water were withheld for the duration of the experiment. The results were compared by Students t test in 20 control rats, who received no indomethacin, and 16 rats at each dose of indomethacin (1, 3, I@ mg/kg). The percentage reductions by indcmethacin or urinary volume (mls/kg) were : 1 mg/kg, ~-12.3 %, p < 0.01 ; 3 mg/kg, A -16,l %, p ~0.005 ; 10 mg/kg, A - 19,6 %, p < 0.001. The percentage reductions by indomethacin of urinary Na (m mol/kg) were : 1 mg/kg, A-8,8 %, p < 0.05 ; A-15,6 % p < 0.005 ; 10 mg/kg, A - 19 %, p < 0.001. 3 mg/kg, These results indicate that prostaglandins can contribute to diuretic activity and that the non-steroidal anti-inflammatory drug indomethacin reduces the efficacy of the loop-blocking diuretic, furosemide, in a dose-dependent manner.
SUPPLEMENT TO VOL. 27
125
DOSE-DEPENDENT REDUCTION BY INDOCETHACIN OF URINARY VOLUME AND SODIUM EXCRETION DURING FUROSEMTDE DIURESIS IN CONSCIOUS SALINE-LOADEP RATS. BARRETT,
C. and RYAN,
M.P.
Department of Pharmacology University College Dublin BELFIELD, DUBLIN 4. Ireland
Prostaglandins may play an important role in the regulation of renal function. There are indications that the action of diuretics, especially loop-blocking diuretics, can be, at least partly, mediated by renal prostaglandins. Administration of some nonsteroidal anti-inflammatory drugs have been reported to reduce the diuretic efficacy and also the antihypertensive action of diuretic drugs. We have investigated the effects of indomethacin, a non-steroidal anti-inflammatory drug, on urinary volume and sodium excretion during furosemide diuresis in conscious saline-loaded rats. Male Wistar rats, matched by weight, were fasted overnight but allowed free access to water. All experiments were carried out at the same time of the day. Indomethacin (0, 1,3, 10 mg/kg) was administered intraperitoneally in Na CO solution (2 mls/kg). 1 hour later furosemide (40 mg/kg) was giv& arally in 0.9 % NaCl (25 mls/ko). Rats were placed in individual metabolism cages and urine was collected for 5 hours. Food and water were withheld for the duration of the experiment. The results were compared by Students t test in 20 control rats, who received no indomethacin, and 16 rats at each dose of indomethacin (1, 3, I@ mg/kg). The percentage reductions by indcmethacin or urinary volume (mls/kg) were : 1 mg/kg, ~-12.3 %, p < 0.01 ; 3 mg/kg, A -16,l %, p ~0.005 ; 10 mg/kg, A - 19,6 %, p < 0.001. The percentage reductions by indomethacin of urinary Na (m mol/kg) were : 1 mg/kg, A-8,8 %, p < 0.05 ; A-15,6 % p < 0.005 ; 10 mg/kg, A - 19 %, p < 0.001. 3 mg/kg, These results indicate that prostaglandins can contribute to diuretic activity and that the non-steroidal anti-inflammatory drug indomethacin reduces the efficacy of the loop-blocking diuretic, furosemide, in a dose-dependent manner.
SUPPLEMENT TO VOL. 27
125