Furosemide-induced vasodilation: importance of the state of hydration and filtration

Abstract

The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects of furosemide because these maneuvers have been reported to blunt the tubuloglomerular feedback in micropuncture studies. In addition, we also used two structurally different nonsteroidal antiinflammatory drugs to assess the importance of prostaglandins to achieve furosemide's renal vasodilatation. Furosemide (5 mg/kg, i.v.) increased renal blood flow in volume-depleted animals from a baseline flow of 141 +/- 28 ml/min to a maximum of 176 +/- 35 ml/min at 6 min after furosemide administration. If the animals were pretreated with a high-salt diet and i.m. DOCA for 5 days, furosemide administration produced no renal vascular effects but still caused a large diuresis, and these dogs still had a responsive renal vascular bed to infused prostaglandin E2. In addition, kidneys rendered non-filtering in volume-depleted animals had no renal vascular response to furosemide. Volume-depleted animals, pretreated with either indomethacin or sodium meclofenamate, did not have a renal vascular response to furosemide although they did have a diuretic response and a responsive renal vasculature to prostaglandin E2. From our data, we hypothesize that the renal vascular response to furosemide is secondary to a tubular mechanism mediated by a vasodilatory prostaglandin. Because furosemide has been shown to disrupt the tubuloglomerular feedback mechanism, and the two maneuvers, DOCA plus salt treatment and lack of filtration, blunt the tubuloglomerular feedback response as well as inhibit the renal vascular response to furosemide, we further hypothesize that furosemide-induced renal vasodilation may be secondary to the disruption of an active tubuloglomerular feedback mechanism.