Effect of noradrenaline on renal sodium and water handling in euhydrated and overhydrated man.
1. The renal effects of incremental doses of intravenously infused noradrenaline were evaluated in normal subjects during two different water loads, 5 ml/kg (n = 6) and 20 ml/kg (n = 9), producing conditions of euhydration and overhydration, respectively. 2. Noradrenaline infusion rates ranged from 0.015 to 0.075 microgram min-1 kg-1. In the euhydrated subjects, noradrenaline caused a dose-dependent fall in urinary sodium excretion and an increase in urinary flow rate. During overhydration similar doses of noradrenaline caused a fall in urinary sodium excretion but a decrease in urinary flow rate. 3. Although there was no detectable change in glomerular filtration rate, a dose-dependent fall in effective renal plasma flow was observed in both hydration states during noradrenaline infusion. 4. Noradrenaline infusion was associated with a dose-dependent increase in proximal tubular sodium reabsorption as assessed by the lithium clearance method. Fractional reabsorption of sodium by the distal nephron was, however, unchanged by noradrenaline in both hydration states. 5. Plasma vasopressin concentration was unchanged by noradrenaline in euhydrated subjects. The renin-angiotensin-aldosterone axis was stimulated by noradrenaline in both euhydrated and overhydrated subjects. 6. Thus we conclude that plasma circulating noradrenaline has a dose-dependent antinatriuretic effect in man. The antinatriuretic effect of noradrenaline is mediated mainly at the proximal tubule in man. We have also shown that during overhydration, noradrenaline decreased urinary flow rate. In contrast, in euhydrated subjects, noradrenaline increased urinary flow rate with no accompanying changes in plasma vasopressin concentration, which suggests a direct effect of noradrenaline on the renal tubular permeability to water.
Lang
C C
CC
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, U.K.
Rahman
A R
AR
Balfour
D J
DJ
Struthers
A D
AD
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D014554:Urination / Q000187:drug effects; D014867:Water / Q000378:metabolism*
D014867:Water; D012964:Sodium; D009638:Norepinephrine