Effect of urodilatin infusion on renal haemodynamics, tubular function and vasoactive hormones.
1. The renal efficacy of urodilatin in humans has only been partly investigated. It is unknown whether intravenously infused urodilatin has an effect on sodium reabsorption in both the proximal and distal part of the nephron. 2. Twelve healthy subjects participated in this double-blind, placebo-controlled study in a cross-over design. They received, in a randomized order, a short term (60 min) infusion of urodilatin in three different doses (10, 20 and 40 ng min-1 kg-1 of body weight) and placebo. Renal haemodynamics were estimated by clearance technique with radioactive tracers, and proximal tubular handling of sodium was evaluated by lithium clearance. 3. The 20 ng min-1 kg-1 dose increased the urinary sodium excretion and urinary flow rate compared with the effects of placebo. It increased the glomerular filtration rate and decreased the effective renal plasma flow. In addition, the dose increased the lithium clearance compared with placebo, but did not significantly change the fractional excretion of lithium. On the other hand, it markedly decreased the distal fractional reabsorption of sodium. It also had a suppressive effect on renin secretion. The systemic arterial blood pressure was unchanged, but the dose increased the pulse rate and the haematocrit. The highest dose (40 ng min-1 kg-1) induced a wide variation in the natriuretic and diuretic responses, probably due to a blood-pressure-lowering effect. 4. We conclude, that the urodilatin dose of 20 ng min-1 kg-1 of body weight was most efficacious in this short-term infusion study, and that it had potent natriuretic and diuretic qualities, probably due to stimulation of the glomerular filtration rate and inhibition of sodium reabsorption in the distal part of the nephron.
Carstens
J
J
Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Denmark.
Jensen
K T
KT
Pedersen
E B
EB
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011674:Pulse / Q000187:drug effects; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D012083:Renin