Responses to furosemide in normotensive and hypertensive subjects

As well as inducing natriuresis, intravenous furosemide increases renal prostanoid synthesis and induces renal vasodilation and a rapid rise in plasma renin activity (PRA). Patients with hypertension have abnormalities in renin release and renal vascular resistance that might be due to abnormalities in renal prostaglandin synthesis. We investigated responses to furosemide and placebo in normotensive (n = 13) and hypertensive (n = 14) subjects. There were no clear differences in PRA, sodium and water excretion, or excretion of prostanoid hydrolysis products (6-ketoprostaglandin F1 alpha and thromboxane B2) after placebo. In the hours after furosemide, 0.5 mg/kg-1, hypertensive subjects excreted more sodium, 189 +/- 13 mEq (mean +/- SE) and 154 +/- 8, and water, 1990 +/- 116 ml and 1614 +/- 109, than normotensive subjects. Excretion rates of creatinine and 6-ketoprostaglandin F1 alpha were much the same. Thromboxane B2 excretion rose in hypertensive subjects and was greater than in normotensive subjects (117.6 +/- 17.2 and 58.3 +/- 8.2 ng). With timed urine samples the excretion rate of 6-ketoprostaglandin F1 alpha and thromboxane B2 increased transiently for 30 min or less, whereas sodium and water excretion rates remained elevated for 4 hr. PRA rose in both groups 10 min after injection but reached a higher level in normotensive subjects. These differences in excretion of prostanoid hydrolysis products likely reflect renal synthesis of prostanoids and may be responsible for functional abnormalities of the kidney of hypertensive patients.