Circadian rhythms in physiologic functions are driven, at the molecular level, by a group of transcription factors that oscillate over a 24 hour period, collectively termed the molecular clock. Within the kidney, it has been shown that the molecular clock directly influences transcription of Na
+
transporters and channels, including ENaC. ENaC is regulated by endothelin-1 (ET-1), via ET
B
receptor activation, in response to high salt intake. Thus, we hypothesized that increases in dietary sodium regulate the renal molecular clock (which in turn would facilitate Na+ homeostasis) through an ET
B
dependent mechanism. To address this question, we examined the effect of high salt (HS) intake on renal clock gene (
Bmal1, Cry1, Per1, Per2
) expression. Control and ET
B
receptor deficient (ET
B
def) rats (a model of elevated renal ENaC) were placed on either HS or normal salt (NS) for two weeks and euthanized every 4 hours beginning at Zeitgeber Time 0 (Lights on). In the inner medulla, HS causes a phase delay in
Bmal1
(Fig 1A) expression in control but not ET
B
def rats (Fig 1B). In addition, HS suppressed the expression of
Cry1
, and
Per2
during the respective acrophase in both control and ET
B
def rats (Fig 1C-1F) with no significant effect on
Per1
. In contrast, no significant difference in the expression of
Bmal1, Cry1, Per2, or Per1
(Fig 1I-1P) was found in response to HS in the renal cortex of either control or ET
B
def. These data indicate that HS feeding desynchronizes the molecular clock within the kidney and provides evidence that peripheral clocks are regulated in a cell type specific manner, even within the same organ.
High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation
