Does endothelin-1 mediate the hypoxemia-induced renal dysfunction in newborn rabbits?
In the newborn rabbit, acute normocapnic hypoxemia increases the renal vascular resistance, leading to renal hypoperfusion and decreased glomerular filtration rate. Endothelin is a potent vasoconstrictor peptide, produced by vascular endothelial cells, which could play a role as a mediator of the hypoxemia-induced renal dysfunction. To test this hypothesis, experiments were performed in 24 anesthetized and mechanically ventilated newborn rabbits. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 newborn rabbits (group 1), a bolus injection of 5 nmol.kg-1 of endothelin caused a marked increase in mean blood pressure and renal vascular resistance leading to a significant fall in glomerular filtration rate (-12 +/- 4%) and renal blood flow (-16 +/- 3%). A second group of animals (n = 8) confirmed the neutralizing activity of the endothelin-1 antiserum in vivo. In spite of pretreatment with endothelin-1 antiserum, hypoxemia induced an increase in renal vascular resistance (+40 +/- 18%; p < 0.05) associated with a significant fall in glomerular filtration rate (-18 +/- 7%) and renal blood flow (-29 +/- 6%) in 8 newborn rabbits (group 3). The present results suggest that endothelin-1 does not mediate the hypoxemia-induced renal changes.
Semama
D S
DS
Service de Pédiatrie, Centre Hospitalier Universitaire Vaudois, Lausanne.
Thonney
M
M
Guignard
J P
JP
D000818:Animals; D000831:Animals, Newborn; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D007275:Injections, Intravenous; D007668:Kidney / Q000503:physiopathology*; D011817:Rabbits; D014655:Vascular Resistance / Q000502:physiology
D016232:Endothelins