Renal responses to furosemide are significantly attenuated in male sheep at 6 months of age following fetal uninephrectomy.
We have previously shown that fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days) in male sheep results in a 30% nephron deficit, reduction in glomerular filtration rate (GFR) and renal blood flow, and elevation in arterial pressure at 6 mo of age. Furthermore, in response to an acute 0.9% saline load, sodium excretion was significantly delayed in uni-x animals leading us to speculate that tubuloglomerular feedback (TGF) activity was reset in uni-x animals. In the present study, we induced TGF blockade by furosemide administration (1.5 mg/kg iv over 90 min) and determined GFR, effective renal plasma flow, and urine and sodium excretion responses in 6-mo-old male sheep. In response to furosemide, a significant diuresis and natriuresis was observed in the sham group; however, the response was significantly delayed and reduced in uni-x animals (both, P(treatment×time) < 0.001). Cummulative urinary and sodium output was significantly less in the uni-x compared with the sham sheep (both, P(treatment×time) < 0.001). GFR was increased in the sham but not the uni-x sheep (P(treatment×time) < 0.0001). In conclusion, the excretory response to furosemide was attenuated in the uni-x sheep, and this suggests a rightward resetting of the TGF operating point. The TGF mechanism is important in the fine tuning of sodium homeostasis and is likely a contributing factor for the dysfunction in sodium regulation we have previously observed in the uni-x animals.
Dept. of Anatomy and Developmental Biology, School of Biomedical Sciences, The Univ. of Queensland, St. Lucia, Australia. r.singh7@uq.edu.au
Reetu R
RR
Singh
Karen M
KM
Moritz
John F
JF
Bertram
Kate M
KM
Denton
D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D005333:Fetus / Q000601:surgery*; D005665:Furosemide / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009392:Nephrectomy; D012079:Renal Circulation / Q000187:drug effects; D012756:Sheep; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology / Q000652:urine
D004232:Diuretics; D012965:Sodium Chloride; D005665:Furosemide