Acute effects of furosemide on blood pressure in functionally anephric, volume-expanded rats

The hypotensive effect of loop diuretics is primarily mediated by a decrease in extracellular fluid volume that follows the intense diuresis. In the present study we investigated whether furosemide (1.25 mg/kg i.v.) can acutely lower blood pressure independently of its diuretic action. The experiments were performed in four groups of male Wistar rats: (a) rats in which furosemide was administered after bilateral ligation of renal vessels and saline (0.9% NaCl at a rate of 0.25 ml/min to a Final volume of 1% of body weight) infusion; (b) rats in which furosemide was injected after bilateral ligation of ureters and saline infusion; (c) rats pretreated with indomethacin (3 mg/kg i.p. for 4 days) in which furosemide was injected after bilateral ligation of ureters and saline infusion; (d) sham-operated rats with intact kidneys. All the groups were compared with appropriate time controls. After furosemide injection, heart rate and blood pressure were serially recorded for 30 min by plethysmography. Hematocrit, plasma 6-keto-prostaglandin F_1α levels and plasma renin activity were measured at baseline and 20 min after furosemide injection. No change in blood pressure followed furosemide administration in rats with ligation of the renal vessels. Conversely, furosemide induced a rapid and significant fall in blood pressure associated with a significant increase in heart rate in rats with ligation of the ureters and rats with intact kidneys. Indomethacin pretreatment prevented the furosemide-induced decrease in blood pressure in rats with ligation of the ureters. Hematocrit and plasma 6-keto-prostaglandin F_1α levels were not affected by furosemide in either group. Furosemide administration increased plasma renin activity in the rats with ligation of the ureters and no indomethacin pretreatment and in rats with intact kidneys. Thus, furosemide lowers blood pressure by a mechanism independent of its diuretic action. This mechanism requires integrity of renal vessels and is blocked by indomethacin.