Effects of renal denervation on sodium balance and renal function during chronic furosemide administration in rats.
In order to investigate whether the renal nerves are involved in the compensatory response of increased renal tubular Na reabsorption, which limits the natriuretic response during chronic furosemide treatment (the "braking phenomenon"), daily Na balance measurements were performed in rats with either renal denervation (DNX) or sham denervation (Sham-DNX) infused i.p. for 5 days with furosemide (Fur) (0.5 mg/hr) or vehicle (Veh) (10 microliters/hr) (n = 8 in each group). Renal denervation reduced renal norepinephrine concentration by 98 to 99%. Average daily Na and water excretion was similar in Fur/DNX and Fur/Sham-DNX animals. Fur treatment increased daily sodium excretion by 75% and daily urine production by 150%. Cumulative Na balance during Fur infusion was significantly lower than in Veh-treated animals. All rats were chronically instrumented and, in order to study intrarenal adjustments to chronic Fur treatment, clearance experiments were performed before and after 5 days of Fur infusion. In comparison with Fur/Sham-DNX, Fur/DNX animals showed no significant changes in mean arterial pressure, heart rate, renal plasma flow, glomerular filtration rate or renal tubular handling of sodium, potassium or lithium. A test dose of amiloride produced no changes in lithium clearance, and the natriuretic and antikaliuretic responses to amiloride were unaltered after 5 days of treatment with either Fur or Veh. In both of the Fur-infused groups, there was a significant increase in hematocrit, as compared with the Veh-treated animals, and a significant reduction in plasma potassium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Petersen
J S
JS
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
DiBona
G F
GF
D000818:Animals; D003714:Denervation; D005665:Furosemide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D007677:Kidney Function Tests; D008094:Lithium / Q000378:metabolism / Q000652:urine; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000378:metabolism / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism* / Q000652:urine
D005665:Furosemide; D008094:Lithium; D012964:Sodium; D012083:Renin; D011188:Potassium