Endothelin ET A Receptor Blockade With Darusentan Increases Sodium and Potassium Excretion in Aging Rats

Endothelin ET A Receptor Blockade With Darusentan Increases Sodium and Potassium Excretion in Aging Rats

This study investigated whether intrarenal endothelin-1(ET-1) contributes to sodium excretion in aged rats. Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET A receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean art...

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Veröffentlicht in:Journal of cardiovascular pharmacology 2006-03, Vol.47 (3), p.456-462
Hauptverfasser: Traupe, Tobias, Ortmann, Jana, Haas, Elvira, Münter, Klaus, Parekh, Niranjan, Hofmann-Lehmann, Regina, Baumann, Karin, Barton, Matthias
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container_end_page 462
container_issue 3
container_start_page 456
container_title Journal of cardiovascular pharmacology
container_volume 47
creator Traupe, Tobias
Ortmann, Jana
Haas, Elvira
Münter, Klaus
Parekh, Niranjan
Hofmann-Lehmann, Regina
Baumann, Karin
Barton, Matthias
description This study investigated whether intrarenal endothelin-1(ET-1) contributes to sodium excretion in aged rats. Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET A receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na + , K + -ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P
doi_str_mv 10.1097/01.fjc.0000211709.10735.32
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Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET A receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na + , K + -ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P &lt;0.001) as well as renin activity ( P &lt;0.05), but had no significant effect on gene expression of ENaC or Na + , K + -ATPase subunits. In aged rats, darusentan treatment increased ion excretion ( P &lt;0.05), reduced cortical gene expression of αENaC and α 1 -Na + , K + -ATPase (both P &lt;0.05), and increased plasma aldosterone levels ( P &lt;0.01). These data demonstrate a decrease of sodium and potassium excretion in aged rats, changes that are partly sensitive to ET A receptor blockade. Treatment with darusentan also reduced cortical expression of αENaC and α 1 -Na + , K + -ATPase and increased plasma aldosterone levels independently of blood pressure, electrolytes, renin activity, or angiotensin converting enzyme activity. 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Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET A receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na + , K + -ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P &lt;0.001) as well as renin activity ( P &lt;0.05), but had no significant effect on gene expression of ENaC or Na + , K + -ATPase subunits. In aged rats, darusentan treatment increased ion excretion ( P &lt;0.05), reduced cortical gene expression of αENaC and α 1 -Na + , K + -ATPase (both P &lt;0.05), and increased plasma aldosterone levels ( P &lt;0.01). These data demonstrate a decrease of sodium and potassium excretion in aged rats, changes that are partly sensitive to ET A receptor blockade. Treatment with darusentan also reduced cortical expression of αENaC and α 1 -Na + , K + -ATPase and increased plasma aldosterone levels independently of blood pressure, electrolytes, renin activity, or angiotensin converting enzyme activity. 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Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET A receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na + , K + -ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P &lt;0.001) as well as renin activity ( P &lt;0.05), but had no significant effect on gene expression of ENaC or Na + , K + -ATPase subunits. In aged rats, darusentan treatment increased ion excretion ( P &lt;0.05), reduced cortical gene expression of αENaC and α 1 -Na + , K + -ATPase (both P &lt;0.05), and increased plasma aldosterone levels ( P &lt;0.01). These data demonstrate a decrease of sodium and potassium excretion in aged rats, changes that are partly sensitive to ET A receptor blockade. Treatment with darusentan also reduced cortical expression of αENaC and α 1 -Na + , K + -ATPase and increased plasma aldosterone levels independently of blood pressure, electrolytes, renin activity, or angiotensin converting enzyme activity. These findings may provide new pathogenetic links between aging and sodium sensitivity.</abstract><pub>Lippincott Williams &amp; Wilkins, Inc</pub><doi>10.1097/01.fjc.0000211709.10735.32</doi></addata></record>
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title Endothelin ET A Receptor Blockade With Darusentan Increases Sodium and Potassium Excretion in Aging Rats
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