Systemic and renal response to salt loading in endothelin-1 knockout mice.
Endothelin-1 (ET-1) knockout mice demonstrate elevated blood pressure, which may be associated with disturbance in central cardiorespiratory regulation. In this study we examined responses to salt loading in ET-1 knockout mice to investigate whether ET-1 is involved in the pathophysiology of salt-sensitive hypertension. Male Edn1+/- heterozygous mice and their wild-type littermates were fed either a high NaCl (8%) or a normal (0.2%) diet for 4 weeks. Systemic blood pressure and tissue ET-1 levels were measured as well as several parameters relating to sodium handling and volume homeostasis. On normal diet, renal ET-1 levels of Edn1+/- mice were about 50% of those of wild-type mice. A high-salt diet caused a significant decrease in renal ET-1 levels by about 50% in both groups. Urine volume, urinary sodium excretion, and FENa in mice on the 8% NaCl diet were significantly higher than those in mice on the 0.2% NaCl diet, whereas there were no differences in circulating plasma volume, serum electrocytes, and creatinine clearance. These responses were similar in Edn1+/- and wild-type mice. Although systemic blood pressure was significantly higher in Edn1+/- mice than in the wild-type, the effect of salt loading on blood pressure was not significant in either Edn1+/- or wild-type mice. We conclude that changes in ET-1 production within a physiologic range do not affect salt sensitivity, although renal ET-1 content is decreased by salt loading.
Morita
H
H
Third Department of Internal Medicine, University of Tokyo, Japan.
Kurihara
H
H
Kurihara
Y
Y
Shindo
T
T
Kuwaki
T
T
Kumada
M
M
Yazaki
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019332:Endothelin-1 / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012079:Renal Circulation / Q000187:drug effects*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D019332:Endothelin-1; D017673:Sodium Chloride, Dietary