Responses of blood pressure and catecholamine metabolism to high salt loading in endothelin-1 knockout mice.
The molecular mechanism responsible for salt sensitivity is poorly understood. Mice heterozygous for the null mutation of the endothelin-1 (ET-1) gene, Edn1, may be a potential tool for studying this mechanism, because they have elevated blood pressure and disturbances in central sympathetic nerve regulation. In the present study, we used this mouse model to examine the degree to which ET-1 contributes to the responses of blood pressure and catecholamine metabolism to high salt loading. Male Edn1+/- heterozygous mice and Edn1+/+ wild-type littermates were given either a high salt (8%) or a normal salt (0.7%) diet for 4 wk. During the normal diet, renal ET-1 levels in Edn1+/- mice were approximately 50% lower than ET-1 levels in wild-type mice, whereas the high salt diet decreased renal ET-1 levels by about 50% in both Edn1+/- and wild-type mice. The high salt diet significantly increased urinary sodium excretion and fractional excretion of sodium (FENa) but did not affect circulating plasma volume, serum electrolytes, creatinine clearance, or systemic blood pressure. In addition, urinary norepinephrine and normetanephrine excretion were significantly increased, indicating that salt loading can increase sympathetic nerve activity in normal mice. These responses to salt loading did not differ between Edn1+/- mice and their wild-type littermates. We conclude that physiological changes in ET-1 production do not affect the responses of blood pressure and catecholamine metabolism to salt loading, although the renal ET-1 content is decreased by salt loading.
Morita
H
H
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan.
Kurihara
H
H
Kurihara
Y
Y
Kuwaki
T
T
Shindo
T
T
Oh-hashi
Y
Y
Kumada
M
M
Yazaki
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002395:Catecholamines / Q000097:blood / Q000652:urine*; D019332:Endothelin-1 / Q000502:physiology*; D005500:Follow-Up Studies; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000097:blood / Q000235:genetics / Q000652:urine; D012964:Sodium / Q000097:blood / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000502:physiology
D002395:Catecholamines; D019332:Endothelin-1; D012982:Sodium, Dietary; D012964:Sodium