Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain

Figures

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  Fig 1. Mean arterial pressure (MAP) of CalOE and tTA control mice fed a standard normal salt diet. MAP of CalOE and tTA mice (A) at 3 hour intervals, (B) during an average 24 hour period, and (C) at night and day across four days (n = 4–5; *, P < 0.05 vs. tTA (daytime); #, P < 0.05 vs. CalOE (daytime); λ, P < 0.05 vs. tTA (nighttime)).

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  Fig 2. Average 24-hour telemetry data for systolic BP (SBP) (A), heart rate (HR)(B) and activity (C) in CalOE and tTA control mice fed a normal salt diet (n = 4–5; *, P < 0.05 vs. tTA).

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  Fig 3. Systolic BP (SBP) measured by tail cuff in CalOE and tTA mice before and after 2-week treatment with DOX. Consistent with telemetry data, SBP was significantly elevated in CalOE relative to controls. However, DOX treatment abolished the difference in SBP between CalOE and tTA mice (n = 5–6; *, P < 0.05).

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  Fig 4. Plasma and excreted catecholamines in urine in CalOE and tTA control mice fed a normal salt diet. (A) Levels of plasma norepinephrine were higher in CalOE mice compared to tTA controls, whereas plasma epinephrine levels were lower. (B) Urinary dopamine excretion levels were lower in CalOE mice compared to controls (n = 5–6; *,P < 0.05).

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  Fig 5. Effect of twelve days of high salt diet on MAP. MAP of CalOE and tTA mice (A) at 3 hour intervals, (B) during an average 24 hour period, and (C) at night and day across four days (n = 4–5; *, P < 0.05 vs. tTA (daytime); #, P < 0.05 vs. CalOE (daytime); λ, P < 0.05 vs. tTA (nighttime)).

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  Fig 6. Effect of high salt diet on proteinuria and TBARs excretion. High salt diet treatment significantly increased proteinuria and TBARs in both groups (A, C); the fold change in proteinuria and TBARs excretion was higher in CalOE mice (B,D) (n = 6; *, P < 0.05 vs. tTA (normal salt); #, P < 0.05 vs. CalOE mice (normal salt); λ, P < 0.05 vs. tTA (high salt)).

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  Fig 7. Effect of high salt diet treatment on renal levels of (A) cytochrome P450 hydrolase (CYP4A), (B) cytochrome P450 epoxygenase (CYP2C44) and (C) soluble epoxide hydrolase (sEH). CYP4A is increased in CalOE by high salt diet challenge. CYP2C44 and sEH expression were elevated in both tTA and CalOE mice compared to levels found in mice on normal salt diet. However, only sEH expression was significantly higher in CalOE compared to tTA mice during high salt loading (n = 3; *, P< 0.05 vs. tTA (normal salt); #, P< 0.05 vs. CalOE (normal salt); λ, P < 0.05 vs. tTA (high salt)).