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Direct and indirect inhibition of the circadian clock protein Per1: effects on ENaC and blood pressure
How direct and indirect blocking of the body’s daily clock protein Per1 affects kidney salt channels and blood pressure
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Abstract
Loss of the circadian clock protein Period 1 (Per1) is associated with protection from hypertension in mice.
- Global Per1 knockout mice on a high-salt diet with mineralocorticoid treatment show reduced hypertension.
- Inhibition of epithelial sodium channels (ENaC) leads to changes in blood pressure regulation and urinary sodium excretion.
- Pharmacological inhibition of Per1 nuclear entry alters the expression of Per1 target genes and lowers blood pressure.
- Genetic knockdown of Per1 in amphibian kidney cells demonstrates decreased activity of ENaC at the single channel level.
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