Acute hypoxia and endogenous renal endothelin.
Endothelin (ET) is a potent vasoconstrictor peptide of endothelial cell origin. Recent studies have suggested a nonvascular paracrine and/or autocrine role for endothelin in the kidney. This study was designed to elucidate the renal ET response to acute moderate hypoxia, as reflected by urinary ET excretory rate and renal tissue ET immunoreactivity, and to correlate these responses to the hemodynamic and excretory changes during hypoxia. Experiments were conducted in two groups of anesthetized dogs: hypoxic group (10% O2 ventilation: PO2, 44 mm Hg; N = 7) and time control group (room air ventilation: PO2, 111 mm Hg; N = 6). After 60 min of hypoxia or room air ventilation, kidneys were harvested and stained immunohistochemically for ET. Acute moderate hypoxia was associated with significant increases in urinary ET excretion, urine flow, urinary sodium excretion, and fractional excretion of sodium (P < 0.05). There was no significant change in GFR, RBF, renal vascular resistance, or mean arterial pressure. Renal immunohistochemistry for ET revealed increased staining in the proximal and distal tubules in the hypoxic group as compared with controls. This study demonstrates that acute moderate hypoxia results in increased urinary ET excretion and renal tubular ET immunoreactivity, in association with diuresis and natriuresis, and suggests a nonvascular role of endogenously produced renal ET in the regulation of sodium homeostasis during hypoxia.
Nir
A
A
Department of Pediatrics, Mayo Clinic and Foundation, Rochester, MN.
Clavell
A L
AL
Heublein
D
D
Aarhus
L L
LL
Burnett
J C
JC
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D016232:Endothelins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006706:Homeostasis; D000860:Hypoxia / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D012964:Sodium / Q000378:metabolism
D016232:Endothelins; D012964:Sodium